SPICE – a previously uncharacterized protein required for centriole duplication and mitotic chromosome congression

Abstract

SummaryProper assembly and function of a bipolar mitotic spindle is crucial for faithful bidirectional chromosome segregation during cell division. In animal cells, the two poles of the mitotic spindle are organized by centrosomes, microtubule-organizing structures composed of a pair of centrioles surrounded by the so-called pericentriolar material. Proteomic studies have revealed a large number of centrosome proteins, but many remain uncharacterized. Here, we characterize SPICE, a protein that localizes to spindle microtubules in mitosis and to centrioles throughout the cell cycle. RNAi-mediated depletion of SPICE in human cells impairs centriole duplication and causes severe mitotic defects. SPICE depletion compromises spindle architecture, spindle pole integrity and chromosome congression, even in cells in which centriole duplication has occurred. Our data suggest that SPICE is an important dual-function regulator required for centriole duplication and for proper bipolar spindle formation and chromosome congression in mitosis.

CEP120 and SPICE1 Cooperate with CPAP in Centriole Elongation

“…Drosophila CEP135 is dispensable for cartwheel formation but is required to maintain robust centriole architecture [35]. It is therefore tempting to speculate that the decrease in the number of centrioles after CEP120 or SPICE1 depletion may be due to the assembly of abnormal/ short procentrioles [23,25]. This would be consistent with a report demonstrating that CEP135-deficient cells have perturbed centriolar triplet MT organization [34].…”

“…We originally identified CEP120 and SPICE1 as putative interacting proteins [23]. While both are required for centriole duplication [23][24][25], CEP120 also participates in neuronal nuclear migration [26], and its loss in planarians results in shorter centrioles [27]. Together, these data suggest that the association between SPICE1 and CEP120 might reflect a shared function in centriole biogenesis.…”

“…CPAP can bind aand b-tubulin dimers through its PN2-3 domain [37] and can regulate the nucleotide status of tubulin [33]. SPICE1 occupies the mitotic spindle, but whether CEP120 or SPICE1 also bind tubulin directly remains unknown [25]. One possibility is that CEP120, CEP135, and CPAP recruit SPICE1 to centrioles, where SPICE1 regulates microtubule stability through an unknown mechanism.…”

The Centrosome and Its Duplication Cycle

“…Overexpression of either CPAP or CEP120 results in excessively long centrioles and their depletion abolishes this phenotype (Comartin et al 2013;Lin et al 2013b). CEP120 also interacts with SPICE1 that is required for centriole duplication, spindle formation, and chromosome congression (Archinti et al 2010). Depletion of SPICE1 also results in short procentrioles, although, in contrast to its partners, overexpression of SPICE1 does not cause centriole elongation (Comartin et al 2013).…”

AIRE is a critical spindle-associated protein in embryonic stem cells

“…The reasons for this are not entirely clear. However, our BioID data suggest that Aire may act in a multi-protein complex, including SPICE1 ( Archinti et al, 2010 ), Human Augmin Complex (HAUS) complex proteins (Haus5 and Haus8) and CLASP proteins (CLASP1 and CLASP2) ( Lawo et al, 2009 ; Bratman and Chang, 2008 ), which have all been reported to function in centrosome maturation/duplication and mitotic spindle organization. Removal of AIRE from the complex by gene knockout could result in a partially functional complex, while replacement with a dominant negative form like AIRE ΔLESLL could disrupt the conformation of that complex and cause a more complete loss of function, as have been shown before in other experimental systems ( Veitia, 2007 ; Papp et al, 2003 ).…”