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Kalirin12 interacts with dynamin

DOI: 10.1186/1471-2202-10-61

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Abstract:

The IgFn domain of Kalirin12, not present in other Kalirin isoforms, binds dynamin1 and dynamin2. An inactivating mutation in the GTPase domain of dynamin diminishes this interaction and the isolated GTPase domain of dynamin retains the ability to bind Kalirin12. Co-immunoprecipitation demonstrates an interaction of Kalirin12 and dynamin2 in embryonic brain. Purified recombinant Kalirin-IgFn domain inhibits the ability of purified rat brain dynamin to oligomerize in response to the presence of liposomes containing phosphatidylinositol-4,5-bisphosphate. Consistent with this, expression of exogenous Kalirin12 or its IgFn domain in PC12 cells disrupts clathrin-mediated transferrin endocytosis. Similarly, expression of exogenous Kalirin12 disrupts transferrin endocytosis in cortical neurons. Expression of Kalirin7, a shorter isoform which lacks the IgFn domain, was previously shown to inhibit clathrin-mediated endocytosis; the GTPase domain of dynamin does not interact with Kalirin7.Kalirin12 may play a role in coordinating Rho GTPase-mediated changes in the actin cytoskeleton with dynamin-mediated changes in membrane trafficking.The human genome encodes sixty-nine GDP/GTP exchange factors (GEFs) for small GTPases of the Rho subfamily [1,2]. All share the ability to remove GDP from target Rho proteins, allowing GTP to bind so that downstream effectors can be activated. In addition to having two RhoGEF domains, the Kalirin/Trio subfamily is unique in its use of multiple protein/protein and protein/lipid interaction modules (Fig. 1A). Kalirin7, the most prevalent isoform in adult brain, begins with a Sec14p domain, includes multiple spectrin-like repeats and ends with a PDZ binding motif. Kalirin7 is concentrated at the post-synaptic density (PSD) and is necessary for spine maturation, maintenance and function [3-7]. Kalirin12, the largest isoform, is most prevalent during embryonic development, but is also present in adult neurons [8,9].Features unique to Kalirin12 inclu

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