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Redundant and distinct functions for dynamin-1 and dynamin-2 isoforms
Y Altschuler1, S M Barbas, L J Terlecky
1Department of Anatomy, University of California, San Francisco, California 94143, USA.
The Journal of Cell Biology
|December 29, 1998
Summary
Dynamin isoforms dynamin-1 and dynamin-2 both inhibit clathrin-mediated endocytosis. However, they function differently at specific cell membrane domains, suggesting specialized roles in vesicle formation.
Area of Science:
- Cell Biology
- Molecular Biology
- Membrane Trafficking
Background:
- Dynamins are essential GTPases involved in vesicle formation.
- Mammals have three dynamin isoforms with distinct tissue expression and splice variants.
- The specific roles of dynamin isoforms in vesicle budding from different organelles remain unclear.
Purpose of the Study:
- To investigate the distinct functions of dynamin-1 and dynamin-2 in endocytosis and biosynthetic transport.
- To resolve conflicting data regarding dynamin-2's role in TGN vesicle budding.
- To compare the effects of dominant-negative mutants of dynamin-1 and dynamin-2 on membrane trafficking.
Main Methods:
- Overexpression of dominant-negative dynamin-1 (dyn1(K44A)) and dynamin-2 (dyn2(K44A)) mutants.
- Assessing effects on receptor-mediated endocytosis in HeLa and polarized MDCK cells.
- Analyzing impact on vesicle budding from the Trans-Golgi Network (TGN).
Main Results:
- Both dyn1(K44A) and dyn2(K44A) potently inhibited receptor-mediated endocytosis.
- Neither mutant directly affected other membrane trafficking events from the TGN.
- Dyn2(K44A) was more potent in HeLa and MDCK basolateral endocytosis; dyn1(K44A) was more potent in MDCK apical endocytosis.
Conclusions:
- Dynamin isoforms have redundant functions in endocytic vesicle formation.
- Dynamin isoforms can be differentially targeted and function in specific plasma membrane subdomains.
- Dynamin-1 and dynamin-2 play distinct, isoform-specific roles in receptor-mediated endocytosis.