(mentions CMT) The SNARE protein SNAP-29 interacts with the GTPase Rab3A:

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J Neurosci Res. 2009 Jan 23. [Epub ahead of print]

The SNARE protein SNAP-29 interacts with the GTPase Rab3A:

Implications for membrane trafficking in myelinating glia.

Schardt A, Brinkmann BG, Mitkovski M, Sereda MW, Werner HB, Nave KA.

Department of Neurogenetics, Max-Planck-Institute of Experimental

Medicine, Göttingen, Germany.

During myelin formation, vast amounts of specialized membrane

proteins and lipids are trafficked toward the growing sheath in cell

surface-directed transport vesicles. Soluble N-ethylmaleimide-

sensitive factor (NSF) attachment proteins (SNAPs) are important

components of molecular complexes required for membrane fusion.

We have analyzed the expression profile and molecular interactions of

SNAP-29 in the nervous system. In addition to its known enrichment in

neuronal synapses, SNAP-29 is abundant in oligodendrocytes during

myelination and in noncompact myelin of the peripheral nervous

system.

By yeast two-hybrid screen and coimmunoprecipitation, we found that

the GTPases Rab3A, Rab24, and septin 4 bind to the N-terminal domain

of SNAP-29. The interaction with Rab24 or septin 4 was GTP

independent.

In contrast, interaction between SNAP-29 and Rab3A was GTP dependent,

and colocalization was extensive both in synapses and in myelinating

glia. In HEK293 cells, cytoplasmic SNAP-29 pools were redistributed

upon coexpression with Rab3A, and surface-directed trafficking of

myelin proteolipid protein was enhanced by overexpression of SNAP-29

and Rab3A.

Interestingly, the abundance of SNAP-29 in sciatic nerves was

increased during remyelination and in a rat model of Charcot-Marie-

Tooth disease, two pathological situations with increased myelin

membrane biogenesis.

We suggest that Rab3A may regulate SNAP-29-mediated membrane fusion

during myelination. (