A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes
Preprint posted on March 22, 2018 https://www.biorxiv.org/content/early/2018/03/22/284901
Article now published in The Journal of Cell Biology at http://dx.doi.org/10.1083/jcb.201803172
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.Binyam Mogessie
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.
Posted on: 8th May 2018Read preprint
Also in the cell biology category:
Antigenic variation by switching inter-chromosomal interactions with an RNA splicing locus in trypanosomes
|Selected by||Mariana De Niz|
KDM6B-dependent chromatin remodelling underpins effective virus-specific CD8+ T cell differentiation
|Selected by||Jonny Coates|
DRP1-mediated regulation of mitochondrial dynamics determines the apoptotic response upon embryonic differentiation
|Selected by||Katarzyna Kuzmicz-Kowalska|
preListscell biology category:in the
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
|List by||Madhuja Samaddar, Ramona Jühlen, Amanda Haage, Laura McCormick, Maiko Kitaoka|
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
|List by||Gautam Dey|
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
|List by||Sandra Malmgren Hill|
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
|List by||Rob Hynds|
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
|List by||Pablo Ranea Robles|
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
|List by||Gautam Dey|
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
|List by||Sandra Franco Iborra|
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
|List by||Joseph Jose Thottacherry|
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
|List by||Gautam Dey, Amanda Haage|