ZW10 interactor (also known as Zwint-1) is part of the MIS12 complex, which is required for kinetochore formation and spindle checkpoint activity []. It recruits ZW10 to unattached kinetochores at prometaphase []. It is essential for stable binding of a Mad1-Mad2 complex to unattached kinetochores []. It can be phosphoryltated by Aurora B (AurB) kinase [].
Zeste white 10 (ZW10) was initially identified as a mitoticcheckpoint protein involved in chromosome segregation, and then implicated in targeting cytoplasmic dynein and dynactin to mitotic kinetochores, but it is also important in non-dividing cells. These include cytoplasmic dynein targeting to Golgi and other membranes, and SNARE-mediated ER-Golgi trafficking [, , ]. Dominant-negative ZW10, anti-ZW10 antibody, and ZW10 RNA interference (RNAi) cause Golgi dispersal. ZW10 RNAi also disperse endosomes and lysosomes [].Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for the proper functioning of the metaphase checkpoint in flies and mammals [, ]. The eukaryotic spindle assembly checkpoint (SAC) monitors microtubule attachment to kinetochores and prevents anaphase onset until all kinetochores are aligned on the metaphase plate. It is an essential surveillance mechanism that ensures high fidelity chromosome segregation during mitosis. In higher eukaryotes, cytoplasmic dynein is involved in silencing the SAC by removing the checkpoint proteins Mad2 and the Rod-Zw10-Zwilch complex (RZZ) from aligned kinetochores [, , ].
The protein Zwilch is an essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. It is required for the assembly of the dynein-dynactin, Mad2 complexes and spindly/CG15415 onto kinetochores [, , ]. Zwilch is a component of the RZZ complex, which is composed of Rod, Zw10 and Zwilch.
This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells [, , ]. TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44 [].
Rod, the Rough deal protein (also known as Kinetochore-associated protein 1) displays a dynamic intracellular staining pattern, localising first to kinetochores in pro-metaphase, but moving to kinetochore microtubules at metaphase. Early in anaphase the protein is once again restricted to the kinetochores, where it persists until the end of telophase. This behaviour is in all respects similar to that described for ZW10 [], and indeed the two proteins function together, localisation of each depending upon the other []. These two proteins are found at the kinetochore in complex with a third, Zwilch, in both flies and humans. The C- terminus is the most conserved part of the protein. During pro-metaphase, the ZW10-Rod complex, dynein/dynactin, and Mad2 all accumulate on unattached kinetochores; microtubule capture leads to Mad2 depletion as it is carried off by dynein/dynactin; ZW10-Rod complex accumulation continues, replenishing kinetochore dynein. The continuing recruitment of the ZW10-Rod complex during metaphase may serve to maintain adequate dynein/dynactin complex on kinetochores for assisting chromatid movement during anaphase[]. The ZW10-Rod complex acts as a bridge whose association with Zwint-1 links Mad1 and Mad2, components that are directly responsible for generating the diffusible 'wait anaphase' signal, to a structural, inner kinetochore complex containing Mis12 and KNL-1AF15q14, the last of which has been proved to be essential for kinetochore assembly in Caenorhabditis elegans. Removal of ZW10 or Rod inactivates the mitotic checkpoint [].
Zeste white 10 (ZW10) was initially identified as a mitotic checkpoint protein involved in chromosome segregation as part of the RZZ (Rod-Zwilch-Zw10) complex, and then implicated in targeting cytoplasmic dynein and dynactin to mitotic kinetochores, but it is also important in non-dividing cells. These include cytoplasmic dynein targeting to Golgi and other membranes, andSNARE-mediated ER-Golgi trafficking in the context of Zw10-Rint1-Nag complex which are DSL11, Tip20, and Sec39 orthologues, respectively [, , ]. Yeast DSL1, is a peripheral membrane protein required for transport between the Golgi and the endoplasmic reticulum, part of the Dsl1p complex (Dsl1Tip20-Sec20-Sec39) [, , ]. These proteins are members of the CATCHR (complexes associated with tethering containing helical rods) family which includes subunits of evolutionarily related complex, such as conserved oligomeric Golgi (COG), Golgi-associated retrograde protein (GARP) and exocyst []. This entry represents the C-terminal domain of Zw10 and DSL1 which consists of an α-helical bundle.
