Search

At the onset of metazoan cell division the nuclear envelope breaks down to enable capture of chromosomes by the microtubule-containing spindle apparatus (1). During anaphase, when chromosomes have separated, the nuclear envelope is reassembled around the forming daughter nuclei (1,2). How the nuclear envelope is sealed, and how this is coordinated with spindle disassembly, is largely unknown. Here we show that endosomal sorting complex required for transport (ESCRT)-III, previously found to promote membrane constriction and sealing during receptor sorting, virus budding, cytokinesis and plasma membrane repair (3-6), is transiently recruited to the reassembling nuclear envelope during late anaphase. ESCRT-III and its regulatory AAA (ATPase associated with diverse cellular activities) ATPase VPS4 are specifically recruited by the ESCRT-III-like protein CHMP7 to sites where the reforming nuclear envelope engulfs spindle microtubules. Subsequent association of another ESCRT-III-like protein, IST1, directly recruits the AAA ATPase spastin to sever microtubules. Disrupting spastin function impairs spindle disassembly and results in extended localization of ESCRT-III at the nuclear envelope. Interference with ESCRT-III functions in anaphase is accompanied by delayed microtubule disassembly, compromised nuclear integrity and the appearance of DNA damage foci in subsequent interphase. We propose that ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly at nuclear envelope-microtubule intersection sites during mitotic exit to ensure nuclear integrity and genome safeguarding, with a striking mechanistic parallel to cytokinetic abscission (7)., Previous studies have shown that ESCRT-III is recruited to the membrane bridge connecting daughter cells during cytokinesis (5,8). Interestingly, cell lines stained with an antibody against the ESCRT-III subunit chromatin [...]

The main organelles of the secretory and endocytic pathways--the endoplasmic reticulum (ER) and endosomes, respectively--are connected through contact sites whose numbers increase as endosomes mature (1-3.) One function of such sites is to enable dephosphorylation of the cytosolic tails of endosomal signalling receptors by an ER-associated phosphatase (4), whereas others serve to negatively control the association of endosomes with the minus-end-directed microtubule motor dynein (5) or mediate endosome fission (6). Cholesterol transfer and [Ca.sup.2+] exchange have been proposed as additional functions of such sites (2,3). However, the compositions, activities and regulations of ER-endosome contact sites remain incompletely understood. Here we show in human and rat cell lines that protrudin, an ER protein that promotes protrusion and neurite outgrowth (7), forms contact sites with late endosomes (LEs) via coincident detection of the small GTPase RAB7 and phosphatidylinositol 3-phosphate (PtdIns(3)P). These contact sites mediate transfer of the microtubule motor kinesin 1 from protrudin to the motor adaptor FYCO1 on LEs. Repeated LE-ER contacts promote microtubule-dependent translocation of LEs to the cell periphery and subsequent synaptotagmin-VII-dependent fusion with the plasma membrane. Such fusion induces outgrowth of protrusions and neurites, which requires the abilities of protrudin and FYCO1 to interact with LEs and kinesin 1. Thus, protrudin-containing ER-LE contact sites are platforms for kinesin-1 loading onto LEs, and kinesin-1-mediated translocation of LEs to the plasma membrane, fuelled by repeated ER contacts, promotes protrusion and neurite outgrowth., The unusual presence of a PtdIns(3)P-binding FYVE domain in the ER protein protrudin (7-10) begged the question as to whether this protein interacts with endosomes, the major PtdIns(3)P-containing organelles in [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tibs.2006.07.009 Byline: Camilla Raiborg, Thomas Slagsvold, Harald Stenmark Abstract: Mono-ubiquitination is a common mechanism of protein regulation, and more than ten ubiquitin-interacting domains that recognize the hydrophobic region centered on Ile44 of ubiquitin have been characterized. Two recent reports describe the crystal structure of the Rab5 guanine-nucleotide-exchange factor Rabex-5 and show that it contains two novel ubiquitin-binding domains. One of these is an A20 zinc finger that binds to a polar interaction interface of ubiquitin centered on Asp58. The discovery of an alternative interaction face of ubiquitin opens new avenues for understanding how this small protein regulates protein function. Author Affiliation: Department of Biochemistry, the Norwegian Radium Hospital and the University of Oslo, Montebello, N-0310 Oslo, Norway

The article presents the discussion on endosome following the degradative pathway or fusing with the plasma membrane to release exosomes. Topics include body fluids such as blood and urine containing exosomes making them useful as biomarkers in cancer; and endosomes vary in the luminal pH, show distinct subcellular localizations, and contain specific proteins and lipids.