Cell polarity is required for the functional specialization of many cell types including lymphocytes. A hallmark of cell polarity is the reorientation of the centrosome that allows repositioning of organelles and vesicles in an asymmetric fashion. The mechanisms underlying centrosome polarization are not fully understood. Here we found that in resting lymphocytes, centrosome-associated Arp2/3 locally nucleates F-actin, which is needed for centrosome tethering to the nucleus via the LINC complex. Upon lymphocyte activation, Arp2/3 is partially depleted from the centrosome as a result of its recruitment to the immune synapse. This leads to a reduction in F-actin nucleation at the centrosome and thereby allows its detachment from the nucleus and polarization to the synapse. Therefore, F-actin nucleation at the centrosome--regulated by the availability of the Arp2/3 complex--determines its capacity to polarize in response to external stimuli.
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http://dx.doi.org/10.1038/ncomms10969 | DOI Listing |
bioRxiv
November 2024
Laboratory of Structural Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Dr., Bethesda, MD, 20892, USA.
SSNA-1 is a fibrillar protein localized at the area where dynamic microtubule remodeling occurs including centrosomes. Despite the important activities of SSNA1 to microtubules such as nucleation, co-polymerization, and lattice sharing microtubule branching, the underlying molecular mechanism have remained unclear due to a lack of structural information. Here, we determined the cryo-EM structure of SSNA-1 at 4.
View Article and Find Full Text PDFSci Adv
December 2024
Laboratory of Cell Cycle Regulation, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500039, India.
Dysfunction of the centrosome, the major microtubule-organizing center of the cell, is implicated in microcephaly. Haploinsufficiency of mixed-lineage leukemia (MLL/KMT2A) protein causes Wiedemann-Steiner syndrome (WSS), a neurodevelopmental disorder associated with microcephaly. However, whether MLL has a function at the centrosome is not clear.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
The centrosome plays a crucial role in facilitating mitotic spindle assembly through its microtubule organizing capacities. Analyzing the composition, structure, and functions of mitotic centrosomes is essential for understanding the mechanisms underlying cell division and centrosome-associated diseases. Isolating centrosomes is an effective method to gain comprehensive information about them while minimizing interference from other cellular components.
View Article and Find Full Text PDFbioRxiv
November 2024
Institute of Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland.
The γ-tubulin ring complex (γ-TuRC) is an essential multiprotein assembly, in which γ-tubulin, GCP2-6, actin, MZT1 and MZT2 form an asymmetric cone-shaped structure that provides a template for microtubule nucleation. The γ-TuRC is recruited to microtubule organizing centers (MTOCs), such as centrosomes and pre-existing mitotic spindle microtubules, via the evolutionarily-conserved attachment factor NEDD1. NEDD1 contains an N-terminal WD40 domain that binds to microtubules, and a C-terminal domain that associates with the γ-TuRC.
View Article and Find Full Text PDFDevelopment
November 2024
Department of Biochemistry and Molecular Biology, University of Iowa, Iowa City, IA 52242, USA.
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