HOPS is an essential constituent of centrosome assembly

Abstract

Centrosomes direct microtubule organization during cell division. Aberrant number of centrosomes results from alteration of its components and leads to abnormal mitoses and chromosome instability. HOPS is a newly discovered protein isolated during liver regeneration, implicated in cell proliferation. Here, we provide evidence that HOPS is an integral constituent of centrosomes. HOPS is associated with classical markers of centrosomes and found in cytosolic complexes containing CRM-1, gamma-tubulin, eEF-1A and HSP70. These features suggest that HOPS is involved in centrosome assembly and maintenance. HOPS depletion generates supernumerary centrosomes, multinucleated cells and multipolar spindle formation leading to activation of p53 checkpoint and cell cycle arrest. The presence of HOPS in cytosolic complexes supports that centrosome proteins might be preassembled in the cytoplasm to then be rapidly recruited for centrosome duplication. Altogether these data show HOPS implication in the control of cell division. HOPS contribution appears relevant to understand genomic instability and centrosome amplification in cancer.

Different functions of HOPS isoforms in the cell

“…In synaptosomes, HOPS has a role in facilitating recycling of GluR2, a subunit of the AMPA receptor. 6 Many functions have been ascribed to HOPS, considered to be a single protein. The current results, however, raise the important question of whether the 3 isoforms of HOPS (lHOPS, iHOPS, and sHOPS) have distinct functions.…”

“…4C and D). 6 The relationship with NPM in the centrosomal formation machinery was similarly tested, obtaining definite evidence in that direction (data not shown).…”

“…We have recently found the 24-kDa isoform is involved in a number of cell functions, participating in centrosome assembly, 6 and being part of a trimeric complex with NPM and p19…”

“…6 For WB analysis, proteins extracted from mouse organs and from COS-1 cells appropriately transfected were separated by SDS-PAGE, transferred to nitrocellulose membrane, and incubated with specific primary antibody in 5% fat-free milk, as previously described.…”

“…1,5 Indeed, HOPS has been identified in cytoplasmic complexes as binding a number of centrosomal proteins that are supposedly centrosomal precursors. 6 HOPS knockdown causes centrosome alteration with hyperamplification and multinucleated cells, and the formation of micronuclei. HOPS is highly expressed in the brain where it putatively acts as a regulator of basal synaptic transmission.…”