Distribution and functions of kinectin isoforms

Abstract

Kinectin is an integral transmembrane protein on the endoplasmic reticulum, binding to kinesin, interacting with Rho GTPase and anchoring the translation elongation factor-1 complex. There has been debate on the specific role(s) of kinectin in different species and cell types. Here we identified 15 novel kinectin isoforms in the mouse nervous system, constituting a family of alternatively spliced carboxy1-terminal variants. Isoform expression is subject to cell type- and developmental stage-specific regulation. We raised specific antibodies to the kinectin variants to characterise their differential intracellular localisation and discovered that certain kinectin isoforms are found in axons where kinectin was previously believed to be absent. We also demonstrated in vivo by overexpression and RNA interference assay that kinectin is selectively involved in the transport of specific types of organelles. A 160 kDa kinectin species is mainly concentrated in the endoplasmic reticulum, anchored via its transmembrane domain and is essential for endoplasmic reticulum membrane extension. A 120 kDa kinectin species is specifically associated with mitochondria, and its interaction with kinesin was found to influence mitochondrial dynamics. These findings contribute to a more unified view of kinectin function. They suggest that different cellular processes use specific kinectin isoforms to mediate intracellular motility and targeting by transient interaction with different motor proteins or other binding partners.