Manasa, C. and Rai, Ashim and Malla, A.B. and Wu, M. and Fiedler, D. and Mallik, R. and Bhandari, Rashna (2016) Inositol hexakisphosphate kinase 1 (IP6K1) activity is required for cytoplasmic dynein-driven transport. Biochemical Journal, 473 (19). pp. 3031-3047. ISSN 0264-6021

Text Biochem J 473 p3031.pdf Restricted to Repository staff only Download (1163Kb) | Request a copy

Abstract

Inositol pyrophosphates such as diphosphoinositol pentakisphosphate (IP7) are conserved eukaryotic signaling molecules that possess pyrophosphate and monophosphate moieties. Generated predominantly by inositol hexakisphosphate kinases (IP6Ks), inositol pyrophosphates can modulate protein function by post-translational serine pyrophosphorylation. Here, we report inositol pyrophosphates as novel regulators of cytoplasmic dynein-driven vesicle transport. Mammalian cells lacking IP6K1 display defects in dynein-dependent trafficking pathways including endosomal sorting, vesicle movement and Golgi maintenance. Expression of catalytically active but not inactive IP6K1 reverses these defects, suggesting a role for inositol pyrophosphates in these processes. Endosomes derived from slime mold lacking inositol pyrophosphates also display reduced dynein-directed microtubule transport. We demonstrate that Ser51 in the dynein intermediate chain (IC) is a target for pyrophosphorylation by IP7 and this modification promotes the interaction of the IC N-terminus with the p150 Glued subunit of dynactin. IC-p150 Glued interaction is decreased and IC recruitment to membranes is reduced in cells lacking IP6K1. Our study provides the first evidence for the involvement of IP6Ks in dynein function and proposes that inositol pyrophosphate-mediated pyrophosphorylation may act as a regulatory signal to enhance dynein-driven transport.

Item Type:	Article
Additional Information:	Open Access from the Publisher
Depositing User:	Users 2 not found.
Date Deposited:	08 Aug 2016 17:39
Last Modified:	21 Oct 2016 08:54
URI:	http://cdfd.sciencecentral.in/id/eprint/740

Actions (login required)

View Item