Spindle assembly requires the coordinated action of multiple cellular structures to nucleate and organize microtubules in a precise spatiotemporal manner. Among them, the contributions of centrosomes, chromosomes, and microtubules have been well studied, yet the involvement of membrane-bound organelles remains largely elusive. Here, we provide mechanistic evidence for a membrane-based, Golgi-derived microtubule assembly pathway in mitosis. Upon mitotic entry, the Golgi matrix protein GM130 interacts with importin α via a classical nuclear localization signal that recruits importin α to the Golgi membranes. Sequestration of importin α by GM130 liberates the spindle assembly factor TPX2, which activates Aurora-A kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GM130, thus linking Golgi membranes to the spindle. Our results reveal an active role for the Golgi in regulating spindle formation to ensure faithful organelle inheritance.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506739PMC
http://dx.doi.org/10.1016/j.cell.2015.06.014DOI Listing

Publication Analysis

Top Keywords

spindle assembly
12
golgi membranes
8
spindle
5
assembly
5
gm130
4
gm130 regulates
4
regulates golgi-derived
4
golgi-derived spindle
4
assembly activating
4
activating tpx2
4

Similar Publications

Delays in mitosis trigger p53-dependent arrest in G1 of the next cell cycle, thus preventing repeated cycles of chromosome instability and aneuploidy. Here we show that MDM2, the p53 ubiquitin ligase, is a key component of the timer mechanism triggering G1 arrest in response to prolonged mitosis. This timer function arises due to the attenuation of protein synthesis in mitosis.

View Article and Find Full Text PDF

CAMSAP2 is required for bridging fiber assembly to ensure mitotic spindle assembly and chromosome segregation in human epithelial Caco-2 cells.

PLoS One

January 2025

Department of Life Science and Medical Bioscience, Laboratory of Cytoskeletal Logistics, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, Japan.

In mammalian epithelial cells, cytoplasmic microtubules are mainly non-centrosomal, through the functions of the minus-end binding proteins CAMSAP2 and CAMSAP3. When cells enter mitosis, cytoplasmic microtubules are reorganized into the spindle composed of both centrosomal and non-centrosomal microtubules. The function of the CAMSAP proteins upon spindle assembly remains unknown, as these do not exhibit evident localization to spindle microtubules.

View Article and Find Full Text PDF

MPS1 kinase is a dual specificity kinase that plays an important role in the spindle assembly checkpoint mechanism during cell division. Overexpression of MPS1 kinase is reported in several cancers. However, drug discovery and development efforts targeting MPS1 kinase did not result in any clinically successful candidates.

View Article and Find Full Text PDF

Cul3 substrate adaptor SPOP targets Nup153 for degradation.

Mol Biol Cell

January 2025

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

SPOP is a Cul3 substrate adaptor responsible for the degradation of many proteins related to cell growth and proliferation. Because mutation or misregulation of SPOP drives cancer progression, understanding the suite of SPOP substrates is important to understanding the regulation of cell proliferation. Here, we identify Nup153, a component of the nuclear basket of the nuclear pore complex, as a novel substrate of SPOP.

View Article and Find Full Text PDF

Satellite DNA shapes dictate pericentromere packaging in female meiosis.

Nature

January 2025

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

The abundance and sequence of satellite DNA at and around centromeres is evolving rapidly despite the highly conserved and essential process through which the centromere directs chromosome inheritance. The impact of such rapid evolution is unclear. Here we find that sequence-dependent DNA shape dictates packaging of pericentromeric satellites in female meiosis through a conserved DNA-shape-recognizing chromatin architectural protein, high mobility group AT-hook 1 (HMGA1).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!