Related Experiment Video

Updated: May 31, 2026

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro
08:53

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro

Published on: January 11, 2017

Common membrane trafficking defects of disease-associated dynamin 2 mutations

Ya-Wen Liu1, Vasyl Lukiyanchuk, Sandra L Schmid

  • 1Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Traffic (Copenhagen, Denmark)
|July 19, 2011
PubMed

Insights

Dynamin 2 (Dyn2) mutations cause disease but don't impair clathrin-mediated endocytosis. Instead, Dyn2 mutants disrupt Golgi export and other endocytosis pathways, potentially explaining tissue-specific diseases.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Dynamin (Dyn) is a GTPase crucial for clathrin-mediated endocytosis (CME).
  • Dyn2 mutations are linked to centronuclear myopathy (CNM) and Charcot-Marie-Tooth (CMT) disease.
  • Disease-associated Dyn2 mutants paradoxically cause slowly progressing, tissue-specific disorders despite ubiquitous Dyn2 expression and essential embryonic roles.

Purpose of the Study:

  • To investigate the cellular defects underlying Dyn2-associated diseases.
  • To characterize the impact of Dyn2 mutants on various membrane trafficking events.
  • To explore potential pathogenic mechanisms for tissue-specific diseases caused by ubiquitous Dyn2.

Main Methods:

  • Utilized mouse Dyn2 conditional knockout cells.
  • Employed retroviral-mediated reconstitution to mimic heterozygous and homozygous Dyn2 mutant states.
  • Quantitatively assessed cellular phenotypes across multiple membrane trafficking pathways.

Main Results:

  • None of the four studied Dyn2 mutants exhibited defects in clathrin-mediated endocytosis (CME).
  • All Dyn2 mutants showed impaired p75/neurotrophin receptor export from the Golgi.
  • Dyn2 mutants were also deficient in raft-dependent endocytosis of cholera toxin and clathrin-independent endocytosis of EGFR.

Conclusions:

  • Dyn2's role in disease pathogenesis may extend beyond CME.
  • Impaired Golgi export and clathrin-independent endocytosis represent potential cellular defects.
  • These defects could explain the tissue-specific nature of Dyn2-related disorders, particularly in muscle and neuronal tissues.

More Related Videos

Quantitative Approaches for Studying Cellular Structures and Organelle Morphology in Caenorhabditis elegans08:47

Quantitative Approaches for Studying Cellular Structures and Organelle Morphology in Caenorhabditis elegans

Published on: July 5, 2019

Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin10:19

Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin

Published on: January 24, 2025

Related Concept Videos

Membrane Asymmetry Regulating Transporters01:19

Membrane Asymmetry Regulating Transporters

Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
The Significance of Membrane Transport01:44

The Significance of Membrane Transport

The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Mechanisms of Membrane-bending01:15

Mechanisms of Membrane-bending

The living membranes are flexible due to their fluid mosaic nature; however, their bending into different shapes is an active process regulated by specific lipids and proteins. The membrane bending can be transient as seen in vesicles or stable for a long time as in microvilli. Cells regulate the size, location, and duration of the membrane curvature.
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Introduction to Membrane Traffic01:44

Introduction to Membrane Traffic

The ER, Golgi apparatus, endosomes, and lysosomes work in tandem to modify, sort, and package proteins and lipids. An integrated membrane trafficking network facilitates the back and forth shuttling of molecules within different organelles in the same cell or across the cell membrane.
The transport of soluble and membrane proteins is mediated by transport vesicles that collect cargo from one cellular compartment and deliver it to another by fusing with the target organelle membrane. The Rab...
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...