Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Membrane Remodeling: Where Yoga Meets Cell Biology

Published: Tuesday, June 11, 2013
Last Updated: Tuesday, June 11, 2013
Bookmark and Share
NIH-funded study reveals protein, fatty molecules and cellular energy work together during endocytosis.

Cells ingest proteins and engulf bacteria by a gymnastic, shape-shifting process called endocytosis. Researchers at the National Institutes of Health revealed how a key protein, dynamin, drives the action.

Endocytosis lets cells absorb nutrients, import growth factors, prevent infections and accomplish many other vital tasks. Yet, despite decades of research, scientists don't fully understand this membrane remodeling process.

New research reveals, on the real-life scale of nanometers, how individual molecules work together during a single act of endocytosis.

"We've discovered new details about a basic process used in all sorts of ways by every cell in the body," said co-author Joshua Zimmerberg, M.D., Ph.D., head of the Program in Physical Biology at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), where the research was conducted. "It's the culmination of a 30-year journey."

The research was led by Vadim Frolov, Ph.D., a former postdoctoral fellow in Dr. Zimmerberg's lab. It appears in a Science paper co-authored by an international team of researchers in the United States, Spain, Russia and India.

In addition to funding Dr. Zimmerberg, NIH also supported the work through a grant from the National Institute of General Medical Sciences (NIGMS) to co-author Sandra Schmid, Ph.D. at the University of Texas Southwestern Medical Center in Dallas. Dr. Schmid is an expert on dynamin.

Scientists have known for years that dynamin plays the major role in endocytosis. After other molecules known as coat proteins pinch the cell's membrane to form an inward-puckering sac, dynamin wraps, python-like, around the neck of the sac and squeezes it tightly.

A jolt of energy from a molecule called GTP severs the neck, releasing a free-floating bubble, called a vesicle, inside the cell, and sealing the cell's outer membrane shut. All the while, neither the cell nor the vesicle leak any of their contents.

Drs. Zimmerberg, Schmid and colleagues discovered how the cell overcomes a seemingly insurmountable energy barrier to accomplish this feat. It's not a matter of brute force, as previously suspected, but something much more zen-like-molecular cooperation.

Neck severing starts when dynamin dips slightly into the pliable cell membrane. Lipids (oily molecules) in the membrane move aside, shifting their tails to accommodate the protein. This molecular crowding stresses the membrane, further constricting the neck of the developing vesicle.

Then GTP finishes the job. But not, as you might expect, with a fatal tug of the dynamin noose. Rather the opposite: Like a yoga instructor, GTP encourages the membrane to relax, despite its extreme stress. In the middle of this state of relaxation, the vesicle suddenly pinches off.

In trying to understand this counterintuitive move, the researchers speculate that GTP melts the inside of dynamin a bit, turning the protein into a flexible scaffold that stabilizes the membrane while the lipids rearrange themselves.

"We see no other way to lower the energy barrier to remodeling without having any leaks," states Dr. Frolov, who formulated the idea.

The researchers also found that, without access to GTP, dynamin will keep growing, twisting three or four times around the neck of the sac. When GTP is present (as is the case in living organisms), it only lets dynamin coil once or twice before it snaps off the vesicle.

All of this information helps scientists better understand a process critical to life.

Genetic defects in endocytosis-and the reverse process, exocytosis-are linked to a host of human diseases, including muscular dystrophy, Alzheimer's disease, leukemia and many others. In addition, some parasites and other pathogens can hijack endocytosis, commandeering the process to enter and infect human cells.

Dr. Zimmerberg is bringing his basic research findings to the clinic. He is studying changes in muscle cell membranes in people who have an adult-onset form of muscular dystrophy. In the disease, the membrane around muscle cells weakens and tears.

Eventually, cells with damaged membranes die, leaking a number of enzymes into the bloodstream. Dr. Zimmerberg hopes to identify changes in blood chemistry that shed light on the disease process and point to possible new treatments. The study soon will begin recruiting patients as volunteers.

This research was supported in part by the intramural program of the NICHD and by NIGMS grant GM42455.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Tuesday, November 10, 2015
Nuclear Transport Problems Linked to ALS and FTD
NIH-supported studies point to potential new target for treating neurodegenerative diseases.
Monday, October 19, 2015
NIH Funding Targets Gaps in Biomedical Research
New awards support emerging issues in cutting-edge biomedical research fields.
Tuesday, October 06, 2015
NIH Framework Points The Way Forward For Developing The President’s Precision Medicine Initiative
The NIH Advisory Committee to the Director has presented to NIH Director Francis S. Collins, M.D., Ph.D., a detailed design framework for building a national research participant group, called a cohort, of 1 million or more Americans to expand our knowledge and practice of precision medicine.
Monday, September 21, 2015
Beth Israel Cardiology Team Awarded $3 Million by NIH
Work will help predict outcomes in patients with heart disease.
Friday, September 18, 2015
Novel Mechanism to Explain Autoimmune Uveitis Proposed
A new study on mice suggests that bacteria in the gut may provide a kind of training ground for immune cells to attack the eye.
Wednesday, August 19, 2015
Nuclear Process in the Brain That May Affect Disease Uncovered
Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease.
Tuesday, August 18, 2015
Scientists Uncover Nuclear Process in the Brain that May Affect Disease
NIH-funded study highlights the possible role of glial brain cells in neurological disorders.
Tuesday, August 18, 2015
PINK1 Protein Crucial for Removing Broken-Down Energy Reactors
NIH study suggests potential new pathway to target for treating ALS and other diseases.
Thursday, August 13, 2015
Tell-tale Biomarker Detects Early Breast Cancer in NIH-funded Study
The study published online in the issue of Nature Communications.
Thursday, August 13, 2015
Researchers Identify Protein in Mice that Helps Prepare for Healthy Egg-sperm Union
Protein RGS2 plays a critical role in preserving the fertilizability of the ovulated egg.
Wednesday, August 05, 2015
Protein Related to Long Term Traumatic Brain Injury Complications Discovered
NIH-study shows protein found at higher levels in military members who have suffered multiple TBIs.
Tuesday, August 04, 2015
Crystal Clear Images Uncover Secrets of Hormone Receptors
NIH researchers gain better understanding of how neuropeptide hormones trigger chemical reactions in cells.
Monday, August 03, 2015
Vital Protein in Healthy Fertilization Process Identified
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice.
Monday, July 27, 2015
NIH Joins Public-Private Partnership to Fund Research on Autism Biomarkers
Biomarkers Consortium project to improve tools for measuring and treating social impairment in children with autism.
Tuesday, July 21, 2015
Scientific News
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Gut Microbes Signal to the Brain When They're Full
Don't have room for dessert? The bacteria in your gut may be telling you something.
Turning up the Tap on Microbes Leads to Better Protein Patenting
Mining millions of proteins could become faster and easier with a new technique that may also transform the enzyme-catalyst industry, according to University of California, Davis, researchers.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Novel Proteins Linked to Huntington's Disease
University of Florida Health researchers have made a new discovery about Huntington's disease, showing that the gene that causes the fatal disorder makes an unexpected "cocktail" of mutant proteins that accumulate in the brain.
Enzyme Critical to Maintaining Telomere Length Discovered
New method expected to speed understanding of short telomere diseases and cancer.
New Method Identifies Up to Twice as Many Proteins and Peptides
An international team of researchers developed a method that identifies up to twice as many proteins and peptides in mass spectrometry data than conventional approaches.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos