Menu

Close

A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes

Pierre ROME, Hiroyuki OHKURA

Preprint posted on March 22, 2018 https://www.biorxiv.org/content/early/2018/03/22/284901

Oocyte problems – a kinesin rises to the challenge. New work shows a kinesin motor delivers microtubule nucleation components to the spindle in fly oocytes. This enables robust assembly of meiotic spindles in the absence of classical centrosomes.

Selected by Binyam Mogessie

Categories: cell biology

Background. When eukaryotic cells divide, a mitotic spindle machinery that is built from the microtubule cytoskeleton equally segregates the chromosomes between daughter cells. In most cell types, this spindle machinery is primarily assembled by the microtubule nucleating activity of centrosomes, which are microtubule-organising centres composed of centrioles. However, in most species, meiotic spindles of oocytes are assembled in the absence of classical centrosomes that contain centrioles. In mouse oocytes, acentriolar microtubule-organising centres play a major role in non-centrosomal spindle assembly. In contrast, microtubule nucleation mediated by the chromosomes themselves predominatly drives spindle assembly in human oocytes. In fly oocytes, a microtubule nucleation mechanism orchestrated by the Augmin complex promotes meiotic spindle assembly. Importantly, loss of the Augmin complex does not prevent meiotic spindle assembly in fly oocytes, which suggests the existence of additional non-centrosomal microtubule nucleation pathways. One candidate, the gamma-tubulin subunit NEDD1 (Grip71 in flies), was implicated in centrosome- and Augmin-independent nucleation of microtubules in oocytes. How NEDD1/Grip71 mediates non-centrosomal meiotic spindle assembly in fly oocytes has remained unknown.

Key findings. Romé and Ohkura now demonstrate that the kinesin motor Mklp2 (Subito in flies) delivers NEDD1/Grip71 to meiotic spindles in oocytes. This allows microtubule nucleation and spindle assembly by the gamma-tubulin complex even in those oocytes that lack Augmin. Indeed, beads containing Mklp2/Subito and NEDD1/Grip71 isolated from oocytes mediate the nucleation of microtubules in cell-free assays. Oocytes therefore appear to have devised yet another solution to the problem of assembling meiotic spindles without centrioles – targeting microtubule nucleation activity to a cellular location of choice via a kinesin motor.

What I like about this work. My lab studies how oocyte spindles that are assembled in the absence of classical centrosomes segregate chromosomes during mammalian meiosis. We suspect that the current list of non-centrosomal spindle assembly pathways in mammalian oocytes may not be complete and that novel mechanisms await discovery. I thus found the preprint from Romé and Ohkura that demonstrates a new mechanism of microtubule nucleation very exciting.

Future directions. This study opens up a number of compelling questions that derserve investigation. We now know why NEDD1/Grip71 (microtubule nucleation activity) recruitment to the spindle critically relies on Augmin during mitosis but not meiosis. Which cues trigger meiosis-specific involvement of a kinesin in this process to allow Augmin-independent NEDD1/Grip71 recruitment (post-translational modifications, expression of an oocyte specific adapter)? The authors show that the N-terminal region of Mklp2/Subito suppresses microtubule nucleation by NEDD1/Grip71 both in oocytes and in vitro. Could this N-terminal region be the target of a meiosis-specific regulatory mechanism that allows Mklp2/Subito-mediated recruitment of microtubule nucleation activity to the spindle? Finally, it will be important to examine whether a similar kinesin-dependent non-centrosomal microtubule nucleation pathway promotes meiotic spindle assembly in oocytes of other species, including mice and humans.

Tags: aneuploidy, centrosomes, chromosome segregation, meiosis, oocyte, spindle

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the cell biology category:

    EFFECTORS OF THE SPINDLE ASSEMBLY CHECKPOINT BUT NOT THE MITOTIC EXIT NETWORK ARE CONFINED WITHIN THE NUCLEUS OF SACCHAROMYCES CEREVISIAE

    Lydia R Heasley, Jennifer G DeLuca, Steven M Markus



    Selected by Hiral Shah

    An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics

    Ilias Angelidis, Lukas M Simon, Isis E Fernandez, et al.



    Selected by Rob Hynds

    1

    Peculiar features of the plastids of the colourless alga Euglena longa and photosynthetic euglenophytes unveiled by transcriptome analyses

    Kristina Zahonova, Zoltan Fussy, Erik Bircak, et al.



    Selected by Ellis O'Neill

    1

    Imaging beyond the super-resolution limits using ultrastructure expansion microscopy (UltraExM)

    Davide Gambarotto, Fabian Zwettler, Marketa Cernohorska, et al.



    Selected by Satish Bodakuntla

    2

    OptoGranules reveal the evolution of stress granules to ALS-FTD pathology

    Peipei Zhang, Baochang Fan, Peiguo Yang, et al.



    Selected by Srivats Venkataramanan

    1

    A new calcium-activated dynein adaptor protein, CRACR2a, regulates clathrin-independent endocytic traffic in T cells

    Yuxiao Wang, Walter Huynh, Taylor Skokan, et al.



    Selected by Nicola Stevenson

    Mitotic chromosome alignment is required for proper nuclear envelope reassembly

    Cindy L Fonseca, Heidi LH Malaby, Leslie A Sepaniac, et al.



    Selected by Maiko Kitaoka

    WNT signaling memory is required for ACTIVIN to function as a morphogen in human gastruloids

    Anna Yoney, Fred Etoc, Albert Ruzo, et al.



    Selected by Sundar Naganathan

    Spatiotemporally controlled Myosin relocalization and internal pressure cause biased cortical extension to generate sibling cell size asymmetry

    Tri Thanh Pham, Arnaud Monnard, Jonne Helenius, et al.



    Selected by Giuliana Clemente

    Nuclear decoupling is part of a rapid protein-level cellular response to high-intensity mechanical loading

    Hamish T J Gilbert, Venkatesh Mallikarjun, Oana Dobre, et al.



    Selected by Rebecca Quelch

    1

    A robust method for transfection in choanoflagellates illuminates their cell biology and the ancestry of animal septins

    David Booth, Heather Middleton, Nicole King



    Selected by Maya Emmons-Bell

    SWI/SNF remains localized to chromatin in the presence of SCHLAP1

    Jesse R Raab, Keriayn N Smith, Camarie C Spear, et al.



    Selected by Carmen Adriaens

    1

    Clathrin plaques form mechanotransducing platforms

    Agathe Franck, Jeanne Laine, Gilles Moulay, et al.



    Selected by Amanda Haage

    Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair

    Jovany Jeomar Franco, Youmna Maryline Atieh, Chase Dallas Bryan, et al.



    Selected by Helen Weavers

    A non-cell autonomous actin redistribution enables isotropic retinal growth

    Marija Matejcic, Guillaume Salbreux, Caren Norden



    Selected by Yara E. Sánchez Corrales

    1

    Rearing temperature and fatty acid supplementation jointly affect membrane fluidity and heat tolerance in Daphnia

    Dominik Martin-Creuzburg, Bret L. Coggins, Dieter Ebert, et al.



    Selected by Alexander Little
    Close

    We want to make our website, and the services we provide, useful and reliable. This sometimes involves placing small amounts of information called cookies on the device you used to access the internet. If you continue to use this website we will assume you are happy to accept our cookies.

    Accept