Powered by Blogger.

Wnt signaling

Tuesday, February 19, 2008

We've discussed Wnt signaling a couple of times before, here, and here.

Wnt refers to a family of proteins now numbering perhaps 20 or more, which have been found in a wide range of multicellular animals, from fruit flies, to fish, to mice and humans. Wnt proteins carry messages between cells, and are especially important in embryogenesis. They are known to play a large role in the control of stem cells and regeneration of body parts (in species where this occurs). In mammals, including humans, Wnt signaling, when it malfunctions, also seems to be involved in many types of cancer, degenerative diseases of aging, and other aging-related problems such as insulin resistance. It may be possible to ameliorate a number of these disease conditions once we have a better understanding of the details of Wnt signaling.

The "Wnt signaling pathway" refers to a sequence of proteins that, in the presence of earlier members of the pathway, change in behavior to affect proteins later in the pathway. The pathway begin when a Wnt protein (secreted by a nearby cell) binds to a cell surface protein, such as the whimsically-named Frizzled. Various other proteins in the pathway then interact, and eventually result in the build-up of a protein called β-catenin, which enters the cell nucleus, where it combines with various transcription factors to affect gene expression.

The name "Wnt" originates from the realization that two genes discovered earlier were homologous – the "wingless" gene in fruit flies (which, when mutated, yields flies without wings), and the Int genes found in mouse tumors.

Although Wnt genes and proteins have now been studied for nearly 20 years, the pace of discovery continues to increase. This is because of the large number of very interesting processes heavily influenced by Wnt signaling – from proliferation and differentiation of stem cells to embryonic development, regeneration of body parts, cancer, and degenerative diseases of aging.

The following summaries of research reports from just the past half year or so will give a buffet-style sample of Wnt-related investigations.

Carbohydrate Regulates Stem Cell Potency (2/1/08)
Embryonic stem cells are characterized by an ability to continually self-renew, but also to give rise to any adult cell type. Stem cell renewal is driven by several external signaling proteins and growth factors, including Wnt, FGF (fibroblast growth factor), and BMP (bone morphogenetic protein). In particular, Wnt signaling stimulates β-catenin to produce the transcription factor Nanog, which maintains pluripotency. However, the ability of these proteins to attach to stem cell surface proteins in order to induce a response seems to depend on the presence of a carbohydrate molecule called heparan sulfate (HS). Stem cells were found to reproduce less frequently but differentiate more frequently in proportion to experimental inhibition of HS production.

Beta-catenin Gradient Linked To Process Of Somite Formation (12/27/07)
In a developing vertebrate embryo somites are masses of a type of tissue (mesoderm) that will eventually develop into such adult tissue types as skeletal muscle and vertebrae. This research on mouse embryos demonstrates the importance of β-catenin as the principal mediator of the Wnt-signaling pathway, in the process of somite formation. In particular, there is a gradient in levels of β-catenin found in cells of the presomitic mesoderm (PSM), and this gradient is critical in regulating mesoderm maturation. This leads to the development of the characteristic vertebral column in embryos of vertebrate animals.

Certain Diseases, Birth Defects May Be Linked To Failure Of Protein Recycling System (12/20/07)
The Wnt signaling protein, like other proteins, is produced in the nuclei of certain cells, and it must be transported to the cell surface, so it can be secreted into the extracellular environment to regulate the growth of tissues during (and after) embryonic development. Another protein, called Wntless (Wls), acts as a cargo container for Wnt, and plays a key role in the transport process. Another protein, called Vps35, which makes up an important part of the "retromer complex", is responsible for moving empty Wls molecules (like freight cars) to where they are needed in the cell. But mutated Vps35 proteins can fail to perform their function, and consequently lead to the failure to transport Wnt out of the cell where it has been produced.

Grape Powder Blocks Genes Linked To Colon Cancer (11/14/07)
Previous research has found that the Wnt signaling pathway is linked to more than 85 percent of sporadic (i. e. not caused by a hereditary defect) colon cancers. Additionally, in vitro studies have shown that resveratrol is capable of blocking the Wnt pathway. The present research showed that in some colon cancer patients who consumed grape powder (which contains resveratrol and possibly other active ingredients), Wnt signaling in biopsied colon tissue was significantly reduced.

Odd protein interaction guides development of olfactory system (10/29/07)
The olfactory system of fruit flies has been shown to develop abnormally when the signaling protein Wnt5 is absent. However, if large amounts of Wnt5 but no Wnt5 receptors called "derailed" are present, development is even more abnormal. Specifically, structures called glomeruli in fruit fly antennal lobes (which are analogous to human olfactory bulbs) grow abnormally when Wnt5 is absent. But if Wnt5 is present in large amounts and there are no derailed receptors, malformed glomeruli develop in locations where they should not be.

Cilia: Small Organelles, Big Decisions (10/3/07)
Research into the development of zebra fish (a favorite of developmental biologists) has shown that organelles called cilia in the cells of developing embryos play a large role in the transduction of Wnt signaling proteins that guide the development process. By blocking the production of three proteins used by cilia, researchers were able to disrupt proper balances in the interpretation of Wnt signals, resulting in developmental defects.

New Insights into the Control of Stem Cells: Keeping the Right Balance (9/15/07)
The Wnt signaling pathway plays a crucial role in embryonic development, cell growth (proliferation), and maturation of cells into specialized cells (differentiation). It is also an important regulator of stem cells. An interaction between Wnt signaling and tyrosine kinases enables the proliferating cells to mature into specialized (differentiated) cells. Normally this interaction strikes a proper balance between proliferation and differentiation. Cancers, such as breast and colon cancer, result when the interaction gets unbalanced. In 90% of human cancers the tumor suppressor APC (adenomatous polypolis coli), one of the core components of the Wnt pathway, is deregulated. This results in excessive amounts of β-catenin, which triggers the onset of breast and colon cancer when it gets into the cell nucleus and affects gene expression.

Reactivating A Critical Gene Lost In Kidney Cancer Reduces Tumor Growth (8/15/07)
Studies of an important tumor-suppressor protein, sFRP-1 (secreted frizzled-related protein 1), in clear cell renal cell carcinoma, the most common type of kidney cancer, may reveal a means to defeat the cancer. sFRP-1 was found to control 13 tumor-promoting genes along the Wnt signaling pathway, which has been linked to a number of cancers, especially colon cancer. Several close relatives of sFRP-1 are also known to affect at least 20 Wnt-related proteins, and up-regulation of members of the sFRP-1 family may be an effective way to control cancers linked to Wnt signaling. In one experiment, increasing sFRP-1 expression in human renal cancer cells was effective, and Wnt regulated oncogenes, such as c-myc, were suppressed compared to untreated cells.

Why Aging Muscles Heal Poorly (8/9/07)
Stem cells normally found in muscle tissue are responsible for repair to muscles damaged by injury or age-related degeneration. But in aged muscle tissue, stem cells tend to produce scar-tissue cells called fibroblasts, instead of normal muscle cells (myoblasts). The overproduction of fibroblasts is a condition known as fibrosis. New research shows that it isn't the age of the muscle stem cells that is the problem, but rather the age of the cellular environment itself, including blood supply to the tissue. The malfunction appears to be a problem with Wnt signaling in the aged environment rather than with the actual stem cells. Muscle stem cells from young mice exhibited the same problems when exposed to an enviroment from older animals.

Related research found that Wnt signaling increased, with detrimental effect, due to age-related deficiency of a hormone called klotho. Klotho seems to inhibit Wnt signaling, and also has some control over insulin sensitivity. However, production of klotho seems to decline with age, possibly leading to age-related problems such as cancer, arterial disease, and insulin resistance.

Not A Relay Race, But A Team Game: New Model For Signal Transduction In Cells (6/27/07)
Details of the inner workings of the Wnt signal transduction process have remained incomplete, but are gradually coming into focus. Member of the Wnt family of proteins may dock with a variety of cell-surface proteins, including LRP6 (low density lipoprotein receptor-related protein 6) and members of the family of G protein-coupled receptors known as Frizzled. After the docking, a signaling cascade is triggered that transmits molecular messages via the cytoplasm to the nucleus. This research shows that the first step after docking involves large protein complexes formed from proteins already known to be part of the signaling pathway, such as phosphorylated LRP6, axin, and Dishevelled (Dvl).

Further reading:

The Wnt Homepage

Regeneration for Repair's Sake

The answer is blowing in the Wnt

Miller on Wnt and Klotho

A hazy shade of Wnt

Tags: , , , , , ,

No comments:

Post a Comment


Knowledge Link Suggest

Drug Abuse Online Lottery Games Drug Abuse Health and Fitness Health and Fitness free music downloads Law Reports Wallpapers Artist online shop originals Product Auto Parts Web Developer online shop originals Product Insurance Company Health Life Technology System Home Security Beauty Cosmetic Online Travel Agency Linux Tips Guide Shooting Simulator Gadgets Technology Project Build Houses Payday Loans Health News Information Animals Shop Travel Agency North Owl Network Dentist Healthy Aging asian pretty The Tool Hospital Barbecook Best way to make Money with Forex Trading Green Home Design Online Lottery atozbythesea.eu.org augmentezvosventes.eu.org automobielbedrijf.eu.org aworldofwindows.eu.org aws-orgware.eu.org azregionalmls.eu.org bacimamma.eu.org Business Plan Competition travel channel and rental cars Pharmacy and drugs Criminal Justice Planning Agency Lawyers Association The Best of Insurance http://celebritytidings.eu.org http://livingandfashion.eu.org Academic Advising Audio logo Stock Audio auto repair advice guide Healthy Women Medical Centre busy with business Car Finance Tools Debt Settlement Lawyer crafty stash corner cuentas and colors Cheap Wedding Dresses drug abuse statistics Lifestyle Home Solutions education essay titles finance insurance premium Lawyer and Legal Information guide healthy recipes health problems of children health topics kids home decorating service home improvement project home improvement project management home improvement project planning home insurance morgages house insurance plan house insurance progressive The Savings Bank insurance agency business loans insurance business loans insurance premium loan legacy landscape blocks legacy landscape contractors legacy landscape materials personal insurance loan real estate for commercial Bedroom Furniture Lawyer Requirements Concept Design teach about alcohol abuse technology support autocar the family deal tile flooring ideas tips lifetime fitness tips reduce car insurance quotes Online Jewelry Stores traveller hotel Insurance and Finance Auto and Parts wood flooring ideas the networks board game Adult Learning Theories sexy lingerie tattoo designs wallpaper artist health category insurance financial category Category Online Money Category Home Improvement online business category Category software games and android category marketing advertising category marketing advertising Home Solution Real Estate Financing Lucepedia Sports and Fitness Train Now Business Economy Global auto car loans car loans insurance Health Information how to prevent diabetes Best Credit Cards Cheap Wedding Dresses Small Business Finance Systems Body Health Home Improvement Services Guide Android Apps and Games fashion design Alcoholism Android Phones Board Games Cheap Tickets and Vacation Packages Online Prevent Child Obesity Prevent Premature Ejaculation Labor Lawyers Home Interior Design Ideas plumbers and carpet cleaning service diet and slimming Beautiful Picture Doctors Dental Care music video art BurningPedia Guide Planning Home Improvement Beauty Cosmetic Web Development Company lawyer requirements Books On Children Education security innovation work iPhone and iPad Turkey The Medical School Barbecue Electric The Linux Documentation Project Mental Health Care New Car Buying Guide House Curtains Dentist All System Education iPhone Specifications Cloud Trading Strategy mortgages and loans Pharmaceutical Info Online Application Service Provider The Masterchef Business Service Delivery Arts and Entertainment Pokerstars Real Money The Masterchef Electric Motors Gadgets Technology Casino Zone Small Business Solutions Home Advice Fashion Design Clothing Adventure Games Health and Fitness Hospital Equipment Plan Life Insurance public transportation services Prevent Premature Ejaculation Best Professional Carpet Cleaning Web Hosting Vehicle Emissions Inspection Drug Abuse Collection Travel Agency Medical Herbs color vision casting Aromatherapy Tips community film Cardio Tips Top Best Home Improvements Article Marketing Colon Cleanse Tips Terms and Conditions of Sale Products for Treating Acne Scars Natural Beauty Products Seo Web Marketing Business Prospects Trade Online Tool House Cleaner Bathing Equipment Financial Solutions Credit Loans Business Insurance Best Supplements Online Affiliate Marketing Web Design Jobs Online Business Degrees Travel and Leisure Hotel Business Online Payment Processor Women Management Criminal Law Marketing Product Webdesign Transportation Services The Marketing Business Prospects Trade Online Shop bed furniture free movies online Direct Hardware Supply Free Download PDF Technology Ipad doctors Specials Medical Dictionary Legacy Landscape Bank South Pacific Carpet Cleaner Best Internet Business Seo Web Marketing Doctor Healthy Doctors Diet Program Health Benefits of Drinking Water ups pills drugs Best Supplements dynasty fine jewelry Ceramic Floor Tile Online Business Degrees Property Residential and Commercial Real Estate All About Medical Bankruptcy Prevent Child Obesity Handbag and Shoes Education of Children physiotherapy school Cheap Airline Tickets Healthy Life PET online Interzoo Rehabilitation Center electric hybrid vehicles Baidu Software Center Automotive Advertising Agencies Health and Care Virtual private network Student Education Technosound Wedding Dresses excel archives Classic Car Restoration Defense Audit Banking Travel and holiday Forex Trading Jobs Cheap Car Insurance Opening the Book Safe Chemical Act Presspeople System Software Plan Life Insurance Top Best Home Improvements Cheap Car Insurance Auto Parts and Service Swiss Business Acting in Real Time Fitness Equipment Tips Bodybuilding Tips Search Engine Optimization Cardio Tips Beauty Salon Express The Best Advice Lawyer Advice Associated With Online Payday Spa and Wellness Center Packages Holiday Travel European Countries Tours Small Business Finance Electronic Cigarette Commercial Law Advice on Travel Planning Home and Family All System Education Graphic Visual Photo business between countries Shop Online Financial Security Authority Latest Fashion Trends Photoshop Wallpaper Real Estate Agents Micro Cogeneration Beauty Products Business Travel Insurance International Trucks For Sale Hair Tonic Top Web Design Business Financial Touring Start Vehicle Emissions Inspection Business Service Delivery Insurance and Finance Web Design Business Shopping Online Insurance Processing Systems Electric System Vehicle Blood Medicine European Vehicle Market Pharmaceutical Section Home sale Beauty Therapy Acupuncture Recipes Kitchen Restaurant Hardwood Flooring Resident Services The Masterchef Employment and the Economy Free Web Design Paint Creations Travel Insurance SEO Consulting Services Car Insurance Loans Doctors Dental Care Vehicle Wash Systems Search Engine Marketing Online Education Schools Natural Beauty Site Cheap Wedding Dresses annuaire automobile episiotomy and pregnant Westerly Lawyers Healthcare Travel Vacations Cheap iPhone Specifications The ReaL Estate Event Online Pharmacy and Drugstore Music Video Art CareCredit Cloud Trading Strategy House Cleaning Services Interoperability the talent agency Good Home Design shooting simulator Independent Port Services The Hotel Sax The Digital Money Booking Tickets and Hotels Online Business Loans Department of Pharmacy Law Free Credit Report football development Trending in Entertainment Prison Education Sexy Lingerie Wood Flooring Ideas Dealer Optics and Ophthalmology Car Insurance Online Urbanism and Architecture Electronic money International Conference on Education Dental Care Auto Repair Shop Auto Repair Advice Guide Dental Clinic Online Pharmacy Debt Consolidation Loans Free Software Smartphone Advice on benefits Insurance Providence Real Estate Product Research Analyst Product Research Facilitator Fashion Magazine Substance Abuse Education And Technology Marketing Strategy The Best Payday Advance Incident Report Criminal Accounting Books Caring for Pets Real Estate Financing Banking Software Solutions Financial Solutions Credit Loans Full Service Research Agency Discover our free games Business Prospects Trade Online Restaurant Hood Cleaning how to start a business Women's Health and Beauty Payday Loans Criminal Attorney Lawyers Travel and Tourism Fashion Designer The Food Products Fitness and Sports The Beginner's Guide to Businesses Tips To Make SEO Techniques Online Payday Loans Medical Advocate Englisch Training Online Drivers Education Auto Parts and Service Best hotels cheap sport shoes Dental Work Insurance Company Android Phones Financial Advice Service Mobile phone Free Credit Report  The Hair Tonic Advantage Car Rental Information Civil Law Information Payday Cash Loans Payday Cash Loans Advance Affordable Auto Insurance Effective Quality Services Car seats Product Interactions Specialist Medicina Natural Traveller and Hotel European Investment Bank Vehicle Electrical System Pet Food Shop Online Lawyer Employment Plaza Ballroom Weddings Art School The best form of insurance solutions Advice on benefits Insurance Medical coding Tutor Buying Safe Products Free Online Game Famous Fashion Designers Education in Music Virtual Currency Systems Learn Trading Folktronica music Digital currency Manufacturing Engineering Technology Fashionista The Money System Explained Good Marketing In Business Technology Ipad Real Estate Bubble CarePass for Android Business Direct Marketing Carpet Cleaner Natural Beauty Products Seo Web Marketing Business Prospects Trade Online Tool House Cleaner Bathing Equipment Financial Solutions Credit Loans Business Insurance Best Supplements Online Affiliate Marketing Web Design Jobs Online Business Degrees Travel and Leisure Hotel Property Residential and Commercial Real Estate All About Medical Bankruptcy Prevent Child Obesity Handbag and Shoes Education of Children Women Management Free Online Slots Games Healthy Life PET online Interzoo Sunrise Health and Rehabilitation Center Presspeople System Software Baidu Software Center Scientific Entrepreneurship Automotive Advertising Agencies Health and Care Virtual private network Student Education Technosound Information network energy sources Niche Dating Classic Car Restoration Defense Audit Banking Travel and holiday Safe Chemical Act Leader in internet information Music Electric The Marketing verb translation country island FILM LITERATURE GOLD STATUS A Short History of Movies Sexy Lingerie Classified ads Inspire Home Design Trauma Clinic Finance Investment Business Marketing Acting in Real Time Glasgow Tourism Herbal Medicine Cheap Car Insurance Quotes Health Pregnancy Professional Graphic and New Media Designers Legal Connect Network Generating Money Online Oregon health plan Slow Cooker Recipes Best Internet Business Terms and Conditions of Sale Products for Treating Acne Scars Hardwoods Furniture Green Tea Fitness Equipment Tips Bodybuilding Tips Forex Trading Article Marketing Colon Cleanse Tips Hair Loss Tips List Building Search Engine Optimization Cardio Tips Aromatherapy Tips Medical Weight Loss Clinic The Benefits Of Moving Insurance Travel Advice Online Dating Security Network Information Green Energy Scheme Group Auto International Business Telecommunication International All Medicine Reviews Marketplace Real Estate Review Clothing Style Management Consulting Real estate Natural Medicine Treatment Natural Beauty Skin Care Products Shop online Marketing Bank rent car guide Fishing Games cheap website traffic Health and Beauty Gambling football Clothes and Accessories Garden and Landscaping Portal Game Online E-commerce Business Car Accident Lawyer Criminal Law Best free Android apps Hotel and Travel Jobs Technology Film Industry Free Music Downloads Solar Installation Search Engine Optimization Life Technologies Football Betting Site Substance Abuse Apartments home improvement contractor job Luxury Car News Law Products and Services Business Web Hosting Company Complaints Diabetes Drug Abuse Marketing Product Make Money Online Living Without Money Apartments Luxury Car News Law Products and Services Growth Technologies Articles on business growth technologies information Health Insurance Management Advisors System Solar Panel Online Trading The Best of Insurance Payday Loans for Bad Credit Financial Solutions Credit Loans Ensure Insurance Plan Financial Management Team Payday Loans Reviews Distributed File System Student Loan Payments Cheap Insurance in Los Angeles Favorite Fashion Styles The Best Savings Rates Manage Student Loans Webshop europe business guide Shop Personal Loans debt consolidation loans Personal Loan Repayment Chiropractic Tables Webdesign Management Concepts Android Software Free Internet Solution the online casino Best Small Business Blogs Sound Beginnings Automotive Electrical Systems Skin Care in Centrum Master Ethique Cher Client Agency Law Sell Products Online Mens Shoes Strategy Business Development Women's shoes Headache Causes Shop Online Clothing Online Pharmacy Healthy Aging Battle Games best electric vehicle Commercial Real Estate Cosmetic Beauty Product Health Medicine Pharmacy Image of the Orient Fashion Jewellery

Blog Archive