In the latest issue of JCB, Wynne and Funabiki reveal that, in the absence of microtubule attachments, a subset of kinetochore proteins form expanded structures that may help activate the spindle checkpoint and capture microtubules. As described in this week’s In Focus, treating Xenopus egg extracts with the microtubule-depolymerizing drug nocodazole causes multiple kinetochore proteins – including the spindle checkpoint regulators BubR1 and Mad1, as well as proteins, such as CENP-E and dynein, involved in lateral microtubule attachment – to form long, thin filaments that extend more than a micron away from the centromeres of mitotic chromosomes.
Kimura et al. describe how TRIM family proteins target specific inflammatory regulators for degradation via the autophagy pathway. As described here, TRIM20 targets several subunits of the inflammasome for degradation by linking them to key autophagy regulators such as ULK1 and Beclin1. TRIM21, on the other hand, links the transcription factor IRF3 – an activator of type I IFN responses – to the autophagy machinery.
Von Büdingen et al. reveal that a component of the myelin sheath surrounding spinal cord axons regulates the growth of neighboring unmyelinated neurons by sequestering NGF. NGF binds with high affinity to a myelin component called MOG, limiting its ability to stimulate the growth of unmyelinated pain-sensing neurons. MOG-deficient mice show increased sprouting of pain-sensing neurons, an observation that could help explain why patients suffering from the demyelinating disease multiple sclerosis often experience chronic neuropathic pain. More here.
Zhou et al. reveal that the disease-related protein progranulin gets a “piggyback” ride to lysosomes by binding to another lysosomal protein, prosaposin. Progranulin, which is mutated in both frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis, can be transported to lysosomes by the sorting receptor sortillin. But, as summarized here, Zhou et al. describe an alternative route, in which prosaposin links progranulin to another sorting receptor, namely the cation-independent mannose 6-phosphate receptor.
Meanwhile, Paul et al. describe how actin spikes drive 3D cell migration, and Lang et al. explain how defects in ER-mitochondrial contacts can be bypassed by other organelle contact sites. We interview the senior authors of both papers in this month’s biobytes podcast; listen below or subscribe in iTunes!
And don’t forget, of course, to check out the issue’s full table of contents by clicking here!
Cover image showing the kinetochore protein BubR1 (magenta) forming extended filaments on Xenopus mitotic chromosomes (blue) © 2015 Wynne and Funabiki.