Intracellular Traffic of Organelles

Re: Specificity of PRD of dynamin

On Thu Dec 10, Leonard Foster wrote
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>Dr. Hussain. Very nice symposium you have presented here. I wonder if you could comment on something I have noticed lately. It seems like everybody and their dog has a protein that will bind dynamin via a PRD/SH3 interaction. I have trouble believing that dynamin has so many endogenous partners. Do you have any idea of the specificity of your intersectin for dynamin (I know if binds SJ but what other PRDs can it bind)? And how do you rationalize so many different partners for dynamin?

>Cheers

>Leonard Foster

Dear Leonard:

You ask a very good series of questions. The specificity of intersectin for dynamin is the easiest one. Intersectin has five SH3 domains. SH3B and SH3D do not interact with dynamin so we have a very nice internal control for in vitro specificity. Intersectin and dynamin co-ip., as do Dap160 (a Drosophila homologue of intersectin and dynamin, Roos and Kelly, JBC). So far, dynamin and synaptojanin are the only proline-rich proteins demonstrated to bind to intersectin.

The rationale for different proline-rich partners for dynamin is difficult to say. Dynamin has an extensive proline-rich C-terminus (as does synaptojanin) with multiple consensus SH3 domain-binding sites. Amphiphysin I and II are certainly important interacters as they are co-localized with dynamin in nerve terminals, they co-ip with dynamin, and regulate dynamin oligomerization. Endophilin may not be an important dynamin interacter as it i.ps. with dynamin very weakly if at all, and the in vitro affinity is much less than the affinity of endophilin for synaptojanin. Grb2 interactions are likely less relevant, especially with dynamin 1 in neurons. Different SH3 partners could control different aspects such as dynamin targeting, oligomerization, enzymatic activity. They may also only be important in specific tissues and stations of the vesicular trafficking pathway, or at specific developmental stages.

Sincerely,

Peter McPherson

Sat Dec 12