The role of motor proteins in endosomal sorting

Abstract

Microtubule motor proteins play key roles in the spatial organization of intracellular organelles as well as the transfer of material between them. This is well illustrated both by the vectorial transfer of biosynthetic cargo from the endoplasmic reticulum to the Golgi apparatus as well as the sorting of secretory and endocytic cargo in the endosomal system. Roles have been described for dynein and kinesin motors in each of these steps. Cytoplasmic dynein is a highly complex motor comprising multiple subunits that provide functional specialization. The family of human kinesins includes over 40 members. This complexity provides immense functional diversity, yet little is known of the specific requirements and functions of individual motors during discrete membrane trafficking steps. In the present paper, we describe some of the latest findings in this area that seek to define the mechanisms of recruitment and control of activity of microtubule motors in spatial organization and cargo trafficking through the endosomal network.

Functional coupling of microtubules to membranes – implications for membrane structure and dynamics

“…In many cases Rab proteins act in concert with other dynein-binding proteins such as bicaudal D homologue (BICD), which acts together with Rab6, or Rab11 family interacting protein 3 (RAB11FIP3), which acts together with Rab11. For further details on the relationship between Rab proteins and motors, see three recent reviews (Allan, 2011;Horgan and McCaffrey, 2011;Hunt and Stephens, 2011).…”

Phosphorylation of CLIP-170 by LRRK1 regulates EGFR trafficking by promoting recruitment of p150Glued to MT plus-ends

“…This endosomal transport determines the intensity and duration of EGFR signaling (Miaczynska et al, 2004;Scita and Di Fiore, 2010). An important determinant of endocytic trafficking is the coupling of endocytic organelles with microtubule-dependent motors (Caviston and Holzbaur, 2006;Soldati and Schliwa, 2006;Akhmanova and Hammer, 2010;Hunt and Stephens, 2011). The minus-end-directed motor dynein is responsible for the early-to-late endosome transport of EGFR along microtubules (Driskell et al, 2007).…”

Noncentrosomal microtubules in C. elegans epithelia

“…Interestingly, vertebrate RAB11, its interacting partner FIP3 and the dynein light intermediate chain DLIC1 form a ternary complex in epidermal carcinoma cells, allowing the transport of cargos from sorting endosomes to the ERC (Horgan et al, 2010;Hunt and Stephens, 2011). As the C. elegans FIP3 homologue was identified in the recycling-endosome-positioning screen mentioned above (Winter et al, 2012), this interaction could be conserved in nematodes.…”