The adaptor proteins HAP1a and GRIP1 collaborate to activate the kinesin-1 isoform KIF5C

Abstract

Binding of motor proteins to cellular cargoes is regulated by adaptor proteins. HAP1 and GRIP1 are kinesin-1 adaptors that have been implicated individually in the transport of vesicular cargoes in the dendrites of neurons. We find that HAP1a and GRIP1 form a protein complex in the brain, and cooperate to activate the kinesin-1 subunit KIF5C in vitro. Based upon this cooperative activation of kinesin-1, we propose a modification to the kinesin activation model that incorporates stabilisation of the central hinge region known to be critical to autoinhibition of kinesin-1.

ARL8 Relieves SKIP Autoinhibition to Enable Coupling of Lysosomes to Kinesin-1

“…This mechanism is analogous to that of several kinesins, whose autoinhibitory, intramolecular interactions are reversed by binding to adaptors or cargos. [26][27][28][29][30][31][32][33][34][35][36][37][38][39] For both SKIP and kinesins, autoinhibition ensures that the proteins exist as inactive forms in the cytosol, preventing futile interactions until they are needed for engagement in cargo movement along microtubules.…”

“…31 The autoinhibition of both KHCs and KLCs is reversed by interaction with cargos or adaptors, activating kinesin-1 for movement along microtubule tracks. 26,[32][33][34][35] Whereas autoinhibitory regulation is well-established for kinesin-1 [26][27][28][29][30][31][32][33][34][35] and other kinesins, [36][37][38][39] to date, it has not been shown to occur for the adaptor proteins that mediate coupling to the corresponding organelles. Herein, we present evidence for such a mechanism for the adaptor protein SKIP ( Figure 1A).…”

DISC1 Regulates Mitochondrial Trafficking in a Miro1-GTP-Dependent Manner

“…COS7 cells were maintained and transfected as described in Twelvetrees et al (2019). Preparation of primary neuronal cultures from E18 pups was performed as previously described (Atkin et al, 2011;Smith et al, 2012Smith et al, , 2014Norkett et al, 2016).…”

The TRIM9/TRIM67 neuronal interactome reveals novel activators of morphogenesis

“…Glutamate receptor interacting protein 1 (GRIP1, TRIM9 FDR: 0, TRIM67 FDR: 0) is a kinesin adaptor protein required for homeostatic AMPA receptor trafficking (Setou et al, 2002;Hoogenraad et al, 2005;Tan et al, 2015;Twelvetrees et al, 2019). Grip1 interacted with both TRIM9∆RING and TRIM67∆RING (Figure3D).…”