TheDrosophilaRZZ complex: roles in membrane traffic and cytokinesis

Abstract

SummaryThe Zw10 protein, in the context of the conserved Rod-Zwilch-Zw10 (RZZ) complex, is a kinetochore component required for proper activity of the spindle assembly checkpoint in both Drosophila and mammals. In mammalian and yeast cells, the Zw10 homologues, together with the conserved RINT1/Tip20p and NAG/Sec39p proteins, form a second complex involved in vesicle transport between Golgi and ER. However, it is currently unknown whether Zw10 and the NAG family member Rod are also involved in Drosophila membrane trafficking. Here we show that Zw10 is enriched at both the Golgi stacks and the ER of Drosophila spermatocytes. Rod is concentrated at the Golgi but not at the ER, whereas Zwilch does not accumulate in any membrane compartment. Mutations in zw10 and RNAi against the Drosophila homologue of RINT1 (rint1) cause strong defects in Golgi morphology and reduce the number of Golgi stacks. Mutations in rod also affect Golgi morphology, whereas zwilch mutants do not exhibit gross Golgi defects. Loss of either Zw10 or Rint1 results in frequent failures of spermatocyte cytokinesis, whereas Rod or Zwilch are not required for this process. Spermatocytes lacking zw10 or rint1 function assemble regular central spindles and acto-myosin rings, but furrow ingression halts prematurely due to defective plasma membrane addition. Collectively, our results suggest that Zw10 and Rint1 cooperate in the ER-Golgi trafficking and in plasma membrane formation during spermatocyte cytokinesis. Our findings further suggest that Rod plays a Golgi-related function that is not required for spermatocyte cytokinesis.

A maternal effectrough dealmutation suggesting multiple pathways regulating Drosophila RZZ kinetochore recruitment

“…However, Mps1, BubR1 and the RZZ complex all participate in other mitotic functions that do not involve the SAC (Starr et al, 1998;Ditchfield et al, 2003;Jones et al, 2005;Lampson and Kapoor, 2005;Maure et al, 2007;Jelluma et al, 2008;Hewitt et al, 2010;Santaguida et al, 2010;Sliedrecht et al, 2010;Althoff et al, 2012;Wainman et al, 2012). It is therefore conceivable that the polar body decondensation is not specifically connected to a defect in SAC activity.…”

What Drosophila spermatocytes tell us about the mechanisms underlying cytokinesis

“…Drosophila Zw10, a subunit of the conserved kinetochore-associated Rod-Zwilch-Zw10 (RZZ) complex required for function of the spindle assembly checkpoint in both Drosophila and mammals (Starr et al, 1998; Scaerou et al, 2001; Williams et al, 2003; reviewed in Karess, 2005; Musacchio and Salmon, 2007), has also recently been shown to play a role in membrane trafficking during cytokinesis in spermatocytes (Wainman et al, 2012). In both mammalian and yeast cells, the Zw10 orthologs form a second complex with the conserved RINT1/Tip20p and NAG/Sec39p proteins that is involved in vesicle transport between Golgi and ER (Hirose et al, 2004; Arasaki et al, 2006; Sun et al, 2007; Varma et al, 2006; Aoki et al, 2009; Schmitt, 2010).…”

“…In Drosophila spermatocytes, Zw10 is enriched at both the Golgi stacks and the ER, and function of Zw10 and the Drosophila homologue of RINT1 are both required for Golgi integrity. Function of both Zw10 and RINT1 is essential for furrow ingression during cytokinesis in spermatocytes (Wainman et al, 2012). In contrast, Rod is required for proper Golgi function, but is dispensable for cytokinesis.…”

Phosphoinositide signaling in sperm development

“…In male germ cells, cytokinesis is incomplete, resulting in formation of stable intercellular bridges that interconnect clonally related cells within a cyst [59] (reviewed in [60]). Because PIPs regulate actin assembly and membrane trafficking, they are ideally suited to orchestrate cytokinesis (reviewed in [61,62] [80,84,86,88] and others remain to be tested.…”

“…Assembly of this structure requires some of the same factors used during meiotic cytokinesis and spermatid cyst elongation: Gio (PITP), Golgi transport factors, Rab11 and Bru (TRAPPII) [68,78,79,81,83,84]. Mutants affecting these proteins exhibit fragmented Golgi and acroblasts rather than Golgi stacks or ribbons.…”