Fewer phosphates but fatter axons

Fewer phosphates but fatter axons xons are fattened by an unexpected neurofilament (NF) subunit, according to Garcia et al. (page 1011) and Rao et al. (page 1021), who find that more phosphorylation sites are not necessarily better when it comes to driving axon expansion. The radial growth-inducing subunit is one of three that make up NFs. The COOH-terminal tails of two of these subunits, NF-H and NF-M, extend perpendicular to the main NF axis and thus bridge NFs with adjacent NFs, actin filaments, or microtubules. These COOH-terminal tails are phosphory-lated in response to myelination, which also initiates a tenfold expansion in volume that is critical for fast conduction of action potentials. As NF-H has 51 phosphorylation sites in its COOH-terminal tail, and NF-M has just 7, NF-H was assumed to be the key phos-phorylation target in axonal expansion, with some researchers suggesting that A The APC–tumor connection hromosomal instability—the less than faithful mitotic segregation of chromosomes—is a hallmark of several cancers, particularly colorectal tumors. Also common in these tumors is a mutation that truncates the adenomatous polyposis coli (APC) protein. On page 949, Green and Kaplan show that this is more than coincidence—APC truncations lead to defective mitotic spindles resembling those of colo-rectal tumor cells. The faulty spindles are a result of defective capture of C microtubule plus ends. The authors expressed the truncated APC protein in noncancerous cell lines that also had normal APC and found that, in these cells, spindle microtubles could no longer grab hold of the kinetochores. This caused chromosome misalignment and segregation defects. Astral microtubules were lost, presumably because they were not stabilized by interactions with the cell cortex. Without complete asters, spindles were free floating and often mispositioned. Similar spindle problems were seen in human colorectal tumor cell lines that have high rates of chromosome instability. Patients are more susceptible to colorectal cancer even when they have only one APC truncation allele. As the truncated product dominantly interfered with plus-end attachments, Kaplan suggests that these individuals might have mitotic abnormalities in intestinal epithelial tissues. He plans to examine spindle morphology in a heterozygous APC mouse model. It is not yet clear how APC makes microtubule plus ends sticky. APC associates with the plus-end binding protein EB1, whose loss phenocopies the APC mutant, so possibly this interaction is necessary for microtubule search and capture. ᭿ Spindles (red) are disrupted by a truncated APC protein (right). …