Mitotic transformation of TRAMM/TrappC12

Intracellular vesicle transport is a mechanism required for the proper targeting and secretion of proteins and lipids. The process comprises sorting, budding, movement, tethering and fusion of the vesicle with the target membrane resulting in delivery of its contents [1]. Transport protein particle (TRAPP) has been demonstrated to contribute to endoplasmic reticulum (ER)-to–Golgi, intra-Golgi and late Golgi anterograde membrane transport as well as autophagy in both yeast and higher eukaryotes. In mammals two related complexes have been described called TRAPP II and TRAPP III [2]. While these complexes share a core of proteins, they each contain unique subunits, some of which are not found in yeast. Alterations of TRAPP subunits have been implicated in human diseases including spondyloepiphyseal dysplasia tarda, limb-girdle muscular dystrophy and a disorder including muscular, intellectual and kinetic phenotypes [3]. Our previous studies implicated the TRAPP subunits TrappC2, TrappC2L, TrappC8, TrappC11 and TrappC12 in an early stage of ER-to-Golgi transport and Golgi integrity [4,5]. Interestingly, several TRAPP complex components have other non-trafficking related functions, perhaps as a result of a TRAPP-independent mode of activity [3]. For example, the core component TrappC4 was implicated in tumorigenesis of colorectal cancer. The protein interacts with ERK2, modulates the nuclear localization of phospho-ERK2 and regulates proliferation and apoptosis in colorectal cancer cells. TrappC4 depletion induces cell cycle arrest in the G0/G1 phase and downregulates the expression of cyclin B1. TrappC9 has been implicated in NF-κB signaling via interactions with both NIK and IKK kinases. In addition, depletion of TrappC9 prevented nerve growth factor-induced neurite outgrowth. Thus, it may not be unexpected if other TRAPP subunits function in non-membrane trafficking processes. Mitosis involves a complex sequence of events that is tightly regulated in space and time and is essential for genome inheritance. It provides accurate chromosome segregation which depends on interactions between microtubules and kinetochores, large protein structures localized at the centromere. CENP-E is a microtubule-dependent plus-end-directed motor expressed during mitosis and essential for congression of initially misaligned chromosomes prior to metaphase. CENP-E binds to a subset of kinetochore proteins that mediate the spindle assembly checkpoint (SAC), a critical mechanism that ensures proper chromosome alignment before anaphase. Disruption of CENP-E function leads to an accumulation of mitotically arrested cells with a population of chromosomes unaligned and in proximity to either of the spindle poles by obstructing microtubule plus-end-directed motion of chromosomes to the metaphase plate and preventing kinetochores from forming stable attachments …