Gli inhibitor pricked by Hedgehog

Augmin-ting the central spindle T he augmin complex generates new micro-tubules in anaphase to build the central spindle and complete cytokinesis, Uehara and Goshima report. The central spindle forms between segregating chromosomes in anaphase and is required for the subsequent cleavage of cells into two daughters. Whether this structure is formed purely by microtubules recycled from the metaphase spindle or whether new microtubules are also needed is unclear. Uehara and Goshima depolymerized existing microtubules in anaphase cells with nocodazole and a low temperature, and saw that new fi laments formed between chromosomes after the drug was removed, generating a functional central spindle from scratch. Fewer microtubules formed in nocodazole-treated cells lacking augmin, a protein complex required for central spindle assembly and cytokinesis. In metaphase cells, augmin amplifi es the number of spindle microtubules by recruiting ␥-tubulin to the mitotic spindle to initiate the assembly of new fi laments. In anaphase, however, the researchers found that augmin builds upon a combination of preexisting fi laments, centrosome-generated microtubules, and/or new fi laments nucleated from chromosomes by the protein HURP. HURP was essential for central spindle formation in anaphase cells treated with nocodazole, but was less important in untreated cells that could reuse their metaphase microtubules as templates for augmin amplifi cation. Without augmin, anaphase cells still assemble some micro-tubules in their central region, but they can't complete cytoki-nesis. Senior author Gohta Goshima now wants to investigate why cell cleavage requires augmin-dependent expansion of the central spindle. Of note, one of augmin's subunits is frequently mutated in breast cancer, potentially causing cytokinesis failure and polyploidy. Y oshimura et al. identify a family of proteins that activate different Rab GTPases at spe-cifi c cell locations to control a variety of membrane traf-fi cking events. There are 63 human Rabs that control membrane transport, but the guanine nucleotide exchange factors (GEFs) that switch each of them on at specifi c times and places are unknown for most family members. The handful of Rab GEFs that have been identifi ed are largely unrelated to one another, although a GEF for Rab3 contains a sequence motif found in several other proteins involved in membrane traffi cking. Yoshimura et al. tested the 17 human proteins with this motif— known as a DENN domain—for their ability to activate Rab proteins. Each DENN protein stimulated distinct Rabs involved in different traffi cking routes. DENND4, for example, activated Rab10, a key …