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 2,600+ scientific posters on ePosters
  • More than 3,800+ 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

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
Mystery of the Tubulin Code Unravelled
NIH study provides a glimpse into the code that controls variety of cell functions.
Wednesday, May 13, 2015
Mouse Study Reveals Potential Clue to Extra Fingers or Toes
NIH-funded study finds that gene appears to regulate protein signals inside the cell.
Tuesday, December 02, 2014
NIH Grant for Texas Biomed to Perform Mass Spec-Based Studies into Heart Disease
Institute awarded $2.7M grant from the NIH to fund innovative approaches to genetics research for the development of new therapies for heart disease and other conditions.
Wednesday, August 20, 2014
Scientific News
Resurrected Proteins Double Their Natural Activity
Researchers demonstrate method for reviving denatured proteins.
Scientists Decode Structure at Root of Muscular Disease
Researchers at Rice University and Baylor College of Medicine have unlocked the structural details of a protein seen as key to treating a neuromuscular disease.
Sniffing Out Cancer
Scientists have been exploring new ways to “smell” signs of cancer by analyzing what’s in patients’ breath.
A New Single-Molecule Tool to Observe Enzymes at Work
A team of scientists at the University of Washington and the biotechnology company Illumina have created an innovative tool to directly detect the delicate, single-molecule interactions between DNA and enzymatic proteins.
Milestone Single-Biomolecule Imaging Technique May Advance Drug Design
The first nanometer resolved image of individual tobacco mosaic virions shows the potential of low-energy electron holography for imaging biomolecules at a single particle level; a milestone in structural biology and a potential new tool for drug design.
Researchers Discover A New Mechanism of Proteins to Block HIV
Certain IFITM proteins block and inhibit cell-to-cell transmission of HIV.
A Natural Light Switch
MIT scientists identify and map the protein behind a light-sensing mechanism.
Biologists Find Unexpected Role for Amyloid-Forming Protein
Yeast protein could offer clues to how Alzheimer’s plaques form in the brain.
Study Adds to Evidence That Viruses Are Alive
A new analysis supports the hypothesis that viruses are living entities that share a long evolutionary history with cells, researchers report.
How Flu Viruses Gain The Ability To Spread
New study reveals the soft palate is a key site for evolution of airborne transmissibility.
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos