However, it is unknown what role the CSF1R plays in microglia homeostasis and viability in the adult brain

ion of either the Nup107 complex or ELYS causes severely defective spindle assembly. This may be due to faulty microtubule polymerisation as the Nup107 complex and ELYS are thought to be important for recruiting the microtubule-nucleating -TuRC complex to spindles. The C terminus of ELYS directly binds to microtubules in a manner dependent on the region containing the AT-hook and a nuclear localization sequence and this binding is inhibited by importin /. Because this inhibition is relieved by RanGTP, ELYS-mediated microtubule nucleation appears to act downstream of the Ran pathway. Similarly, in human cells, ELYS and the Nup107 complex contribute to kinetochore microtubule 139504-50-0 web assembly through recruiting the -TuRC complex to kinetochores. In addition, ELYS and the Nup107 complex may support the centromeric localization of the CPC. It is also noteworthy that in plant prophase cells, the outer nuclear envelope is capable of nucleating microtubules and coordinating bipolar spindle assembly before nuclear envelope breakdown. Thus, in plants, NPCs may also help assemble spindle microtubules in the vicinity of chromosomes. The functional interaction between this nucleoporin pathway and the Ran/CPC pathway would provide further spatial coordination. Author Manuscript Author Manuscript Author Manuscript Author Manuscript General principles and functional implications The observation that nucleosomes are the central platform for spindle and NPC assembly highlights an important regulatory principle by which local and temporal regulation coincide to specify intracellular architecture. Both processes require nucleosomes to recruit RCC1 to chromosomes, thus generating a high local concentration of RanGTP. Depending on the cell cycle stage, however, nucleosomes also acquire specific regulators: ELYS recruitment in interphase contributes to NPC formation, and Aurora B activation by H3T3ph in mitosis supports spindle microtubule polymerisation. Aurora B activation, in turn, needs to be undone for proper NE formation. Why are these processes coupled to nucleosomes, rather than directly to DNA We envisage two non-mutually exclusive possibilities. First, the coupling of NE formation to nucleosomes may be crucial to provide timing in early embryonic development, as male pronucleus formation requires PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19854301 the loading of histones. Second, coupling NE assembly to nucleosomes, rather than naked DNA, may be a quality-control mechanism against NE formation on aberrant DNA in the cytoplasm. For example, many pathogens such as viruses and intracellular bacteria can give rise to cytoplasmic DNA. Certain cell types such as phagocytes are furthermore expected to carry a heavy burden of exogenous DNA, resultant from the phagocytosis of extracellular pathogens, or apoptotic and necrotic cells. Cytoplasmic DNA may also arise from endogenous sources such as retroelements or excessive amounts of DNA damage. Lastly, nucleosomes can be removed from Bioessays. Author manuscript; available in PMC 2016 October 01. Zierhut and Funabiki Page 11 chromatin on anaphase bridges, which can be caused by multiple defects in mitosis. In this respect, it is of interest that chromatin trapped on anaphase bridges as well as lagging chromosomes frequently give rise to micronuclei, on which NEs form only very poorly. It is believed that, as a result of NE aberrations, replication is defective in these micronuclei, leading to massive amounts of DNA damage. In healthy cells, the resulting cell cycle a