The familial cylindromatosis tumor suppressor CYLD is known to contain three cytoskeleton-associated protein glycine-rich (CAP-Gly) domains, which exist in a number of microtubule-binding proteins and are responsible for their association with microtubules. However, it remains elusive whether CYLD interacts with microtubules and, if so, whether the interaction is mediated by the CAP-Gly domains. In this study, our data demonstrate that CYLD associates with microtubules both in cells and in vitro, and the first CAP-Gly domain of CYLD is mainly responsible for the interaction. Knockdown of cellular CYLD expression dramatically delays microtubule regrowth after nocodazole washout, indicating an activity for CYLD in promoting microtubule assembly. Our data further demonstrate that CYLD enhances tubulin polymerization into microtubules by lowering the critical concentration for microtubule assembly. In addition, we have identified by wound healing assay a critical role for CYLD in mediating cell migration and found that its first CAP-Gly domain is required for this activity. Thus CYLD joins a growing list of CAP-Gly domain-containing proteins that regulate microtubule dynamics and function.

The synaptonemal complex (SC) is an ultrastructurally conserved proteinaceous structure that holds homologous chromosomes together and is required for the stabilization of pairing interactions and the completion of crossover (CO) formation between homologs during meiosis I. Here, we identify a novel role for a central region component of the SC, SYP-4, in negatively regulating formation of recombination-initiating double-strand breaks (DSBs) via a feedback loop triggered by crossover designation in C. elegans. We found that SYP-4 is phosphorylated dependent on Polo-like kinases PLK-1/2. SYP-4 phosphorylation depends on DSB formation and crossover designation, is required for stabilizing the SC in pachytene by switching the central region of the SC from a more dynamic to a less dynamic state, and negatively regulates DSB formation. We propose a model in which Polo-like kinases recognize crossover designation and phosphorylate SYP-4 thereby stabilizing the SC and making chromosomes less permissive for further DSB formation.DOI: http://dx.doi.org/10.7554/eLife.23437.001

The proteinaceous zipper-like structure known as the synaptonemal complex (SC), which forms between pairs of homologous chromosomes during meiosis from yeast to humans, plays important roles in promoting interhomolog crossover formation, regulating cessation of DNA double-strand break (DSB) formation following crossover designation, and ensuring accurate meiotic chromosome segregation. Recent studies are starting to reveal critical roles for different protein modifications in regulating SC dynamics. Protein SUMOylation, N-terminal acetylation, and phosphorylation have been shown to be essential for the regulated assembly and disassembly of the SC. Moreover, phosphorylation of specific SC components has been found to link changes in SC dynamics with meiotic recombination. This review highlights the latest findings on how protein modifications regulate SC dynamics and functions.

Oriented cell division is critical for cell fate specification, tissue organization, and tissue homeostasis, and relies on proper orientation of the mitotic spindle. The molecular mechanisms underlying the regulation of spindle orientation remain largely unknown. Herein, we identify a critical role for cylindromatosis (CYLD), a deubiquitinase and regulator of microtubule dynamics, in the control of spindle orientation. CYLD is highly expressed in mitosis and promotes spindle orientation by stabilizing astral microtubules and deubiquitinating the cortical polarity protein dishevelled. The deubiquitination of dishevelled enhances its interaction with nuclear mitotic apparatus, stimulating the cortical localization of nuclear mitotic apparatus and the dynein/dynactin motor complex, a requirement for generating pulling forces on astral microtubules. These findings uncover CYLD as an important player in the orientation of the mitotic spindle and cell division and have important implications in health and disease.O rientation of the cell division axis offers a critical mechanism for the control of cell type choices and the specification of tissue/organ architecture; this is achieved through accurate orientation of the mitotic spindle relative to the cell cortex (1). Spindle orientation is exquisitely regulated during development as well as in adult life, and defects in this process may have severe consequences, such as developmental disorders and tumor formation (1, 2). A dividing cell can orient its spindle along the planar axis or the apicobasal axis of the tissue, depending on the tissue environment and cell geometry. In most epithelia, such as the intestine crypt epithelium, planar spindle orientation is common to produce two daughter cells side by side. By contrast, apicobasal spindle orientation is frequently associated with asymmetric cell divisions, which result in two daughter cells of distinct identities (2).Astral microtubules play a key role in spindle orientation by linking the spindle to the cell cortex (3). The localization of cell polarity proteins such as dishevelled (Dvl) at the cell cortex is also important for spindle orientation by transmission of extrinsic signals or providing the intrinsic cues. Cortical polarity proteins can recruit the nuclear mitotic apparatus (NuMA) protein and then the microtubule minus end-directed dynein/ dynactin motor complex, which can generate pulling forces on astral microtubules to rotate the spindle (3). Therefore, the dynamic interaction of astral microtubules with the cell cortex via diverse protein complexes constitutes an essential part of the mechanism for spindle orientation. However, it remains elusive how the protein complexes controlling spindle orientation are assembled and activated to make a connection between astral microtubules and the cell cortex.As a posttranslational modification, protein ubiquitination is critical for diverse cellular and biological events, and it is a reversal process mediated by E3 ubiquitin ligases and deubiquitinases, respecti...