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The dynamin superfamily: universal membrane tubulation and fission molecules?

Nature Reviews Molecular Cell Biology volume 5, pages 133–147 (2004)Cite this article

Key Points

  • Classical dynamins belong to a superfamily that includes dynamin-like proteins, optic atrophy 1 (OPA1), mitofusin and Mx proteins.

  • On the basis of sequence homology, domain structure and biological functions, we define the superfamily members from yeast and plants to man.

  • It is proposed that all members of the superfamily are membrane-binding and oligomerization-dependent GTPases.

  • On the basis of structural and biochemical comparison, it is possible to test the functions of all members of this superfamily with the use of site-directed mutagenesis.

  • It is proposed that all dynamin-superfamily members are mechanochemical GTPases that either function in membrane scission or tubulation.

  • The mechanochemical mechanism of dynamin is applied to all known biological functions of the superfamily: vesicle scission, mitochondrial fission and fusion, cytokinesis and antiviral activity.

Abstract

Dynamins are large GTPases that belong to a protein superfamily that, in eukaryotic cells, includes classical dynamins, dynamin-like proteins, OPA1, Mx proteins, mitofusins and guanylate-binding proteins/atlastins. They are involved in many processes including budding of transport vesicles, division of organelles, cytokinesis and pathogen resistance. With sequenced genomes from Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans, yeast species and Arabidopsis thaliana, we now have a complete picture of the members of the dynamin superfamily from different organisms. Here, we review the superfamily of dynamins and their related proteins, and propose that a common mechanism leading to membrane tubulation and/or fission could encompass their many varied functions.

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Figure 1: Dynamin-superfamily members in animals and plants.
Figure 2: Domain structure of the human dynamin superfamily.
Figure 3: GTP-binding motifs.
Figure 4: Oligomerization of dynamins.
Figure 5: Functions of dynamins.
Figure 6: GTPase activity and lipid distortion.

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Authors and Affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    Gerrit J. K. Praefcke & Harvey T. McMahon

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Related links

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DATABASES

Flybase

Fzo1

shibire

Interpro

amphyphysin

dynamin

Saccharomyces genome database

Mgm1

Vps1

Schizosaccharomyces pombe GeneDB

Msp1

Swiss-Prot

atlastin

DymA

GBP1

Mammalian dynamin 1

Mammalian dynamin 2

Mammalian dynamin 3

mitofusin

MxA

MxB

OPA1

Ras

TAIR

ADL2

ADL6

ARC5

FURTHER INFORMATION

Dynamin homepage

Dynamin web site

GTPase domain web site

Dynamin assembly

PH domain web site

PRD domain web site

DymA/GBP structures

GTP-binding motifs web site

GTP-binding residues web site

Shibire web site

Oligomerization web site

The OMIM OPA1 entry

More dynamin information

Mx proteins

Glossary

SCISSION

Cleavage of the vesicle from the parent membrane — as in the use of scissors to sever.

SNARE

(soluble N-ethylmaleimide-sensitive fusion protein attachment protein (SNAP) receptor). SNARE proteins are a family of membrane-tethered coiled-coil proteins that regulate fusion reactions and target specificity in vesicle trafficking. They can be divided into v-SNAREs and t-SNAREs on the basis of their localization.

CLASSICAL DYNAMINS

Dynamins that show sequence homology to the protein described in 1989 as 'dynamin', a microtubule-binding protein. For these classical proteins, the homology extends over the complete length of the protein and they have five distinct domains.

DYNAMIN-RELATED PROTEINS

Dynamins that lack one or more domains or have additional domains that are not present in classical dynamins. Some of these proteins might be functionally indistinguishable from classical dynamins.

CLATHRIN-COATED VESICLE

(CCV). Transport vesicles that bud with the aid of a coat protein known as clathrin.

CAVEOLAE

Flask-shaped invaginations of the plasma membrane that are coated with the protein caveolin. Caveolae are endocytosed in a clathrin-independent manner.

DYNAMINS

Members of the dynamin superfamily, which include the dynamin-related proteins, Mx proteins and GBP/atlastin.

PLECKSTRIN-HOMOLOGY (PH) DOMAIN

A protein module of ∼100 amino acids that is present in a range of proteins. Different PH domains interact with various phospholipids and are therefore involved in the targeting of the proteins.

SRC-HOMOLOGY-3 (SH3) DOMAIN

A protein module of ∼80 amino acids that is present in a range of proteins and was first identified in the protein kinase Src. SH3 domains interact with proline-rich sequences that usually contain a PxxxPxR motif.

CLATHRIN-COATED PIT

(CCP). The initial site of invagination of a clathrin-coated vesicle.

FISSION

The breakage of one object into parts — for example, fission of the lipid membrane.

PHRAGMOPLASTIN

Dynamin-like protein found at the phragmoplast, which is the microtubular network in dividing plant cells that transports Golgi-derived vesicles to the cell plate.

CELL PLATE

A flat, membrane-bound incipient cell wall at the division plane of a plant cell. The cell plate is formed by fusion and tubulation of Golgi-derived vesicles, which results in the outward expansion, and finally fusion, of the vesicles with the side walls.

ACTIVE ZONE

A specialized area of the presynaptic plasma membrane where synaptic vesicles fuse and release their neurotransmitter content.

SWITCH REGIONS

Regions of nucleotide-binding proteins that have different conformations in the triphosphate- compared to the diphosphate-bound state.

CRISTAE

The inward folds of the inner mitochondrial membrane that increase its surface area.

PLASTIDS

Organelles that are found in eukaryotic plant cytoplasm. They all contain DNA and are surrounded by a double membrane.

RNA INTERFERENCE

(RNAi). A form of post-transcriptional gene silencing in which expression or transfection of double-stranded RNA induces degradation — by nucleases — of the homologous endogenous transcripts. This mimics the effect of the reduction, or loss, of gene activity.

CLEAVAGE FURROW

An invagination of the plasma membrane in the division plane of an animal cell that contains a contractile ring, and which leads to scission of the daughter cells.

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Praefcke, G., McMahon, H. The dynamin superfamily: universal membrane tubulation and fission molecules?. Nat Rev Mol Cell Biol 5, 133–147 (2004). https://doi.org/10.1038/nrm1313

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