The dynein adaptor Hook2 plays essential roles in mitotic progression and cytokinesis

Abstract

Hook proteins are evolutionarily conserved dynein adaptors that promote assembly of highly processive dynein–dynactin motor complexes. Mammals express three Hook paralogs, namely Hook1, Hook2, and Hook3, that have distinct subcellular localizations and expectedly, distinct cellular functions. Here we demonstrate that Hook2 binds to and promotes dynein–dynactin assembly specifically during mitosis. During the late G2 phase, Hook2 mediates dynein–dynactin localization at the nuclear envelope (NE), which is required for centrosome anchoring to the NE. Independent of its binding to dynein, Hook2 regulates microtubule nucleation at the centrosome; accordingly, Hook2-depleted cells have reduced astral microtubules and spindle positioning defects. Besides the centrosome, Hook2 localizes to and recruits dynactin and dynein to the central spindle. Dynactin-dependent targeting of centralspindlin complex to the midzone is abrogated upon Hook2 depletion; accordingly, Hook2 depletion results in cytokinesis failure. We find that the zebrafish Hook2 homologue promotes dynein–dynactin association and was essential for zebrafish early development. Together, these results suggest that Hook2 mediates assembly of the dynein–dynactin complex and regulates mitotic progression and cytokinesis.

Dynein activators and adaptors at a glance

“…Like BICDR1, Hook3 can interact with two dimeric dynein motors per dynactin (Urnavicius et al, 2018;Grotjahn et al, 2018). In mammalian cells, Hook2 is thought to function at the centrosome and during mitotic progression (Szebenyi et al, 2007;Moynihan et al, 2009;Guthrie et al, 2009;Dwivedi et al, 2019), while Hook1 and Hook3 have been implicated in a variety of endosomal trafficking pathways (Luiro et al, 2004;Maldonado-Báez et al, 2013;Xu et al, 2008;Walenta et al, 2001;Guo et al, 2016), similar to the role of fungal Hook proteins (Zhang et al, 2014;Bielska et al, 2014). Most recently, Hook1 has been shown to be required for the transport of TrkB-BDNF-containing signaling endosomes in neurons, a role specific for Hook1 but not Hook3 (Olenick et al, 2019) (see poster).…”

The Generation of Dynein Networks by Multi-Layered Regulation and Their Implication in Cell Division

“…The recruitment of dynein to the plus end of the microtubules depends on dynactin and EBs, and contributes to the initiation of transport (Moughamian and Holzbaur, 2012;Barbosa et al, 2017;Jha et al, 2017). HOOK proteins recruit dynein to the early endosomes and nuclear envelope (Bielska et al, 2014;Zhang et al, 2014;Guo et al, 2016;Dwivedi et al, 2019). The C. elegans hook protein, ZYG-12, mediates the essential attachment between the centrosome and nucleus (Malone et al, 2003;Minn et al, 2009), and thus plays a critical role in transporting the centrosome/nucleus complex.…”

miR‐496 remedies hypoxia reoxygenation–induced H9c2 cardiomyocyte apoptosis via Hook3‐targeted PI3k/Akt/mTOR signaling pathway activation

“…[11][12][13][14][15] Hooks, with their separate subcellular localizations, naturally exhibit distinct cellular functionality. [11][12][13][14][15] Hooks, with their separate subcellular localizations, naturally exhibit distinct cellular functionality.…”