HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development
Marisa Connell1, Helen Chen1, Jihong Jiang1
1Department of Paediatrics, University of British Columbia, Vancouver, Canada.
Elife
|October 11, 2017
Summary
Hyaluronan-mediated motility receptor (HMMR) is crucial for progenitor cell division orientation. This protein regulates spindle positioning, ensuring proper neural development and tissue homeostasis.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Oriented cell division is vital for development and tissue maintenance.
- Asymmetric cortical NuMA-dynein complexes typically regulate mitotic spindle positioning.
Purpose of the Study:
- To investigate the role of HMMR in progenitor cell division and spindle orientation.
- To elucidate the molecular pathway involving HMMR, PLK1, Ran, and NuMA-dynein complexes.
Main Methods:
- Creation and analysis of Hmmr-knockout mice.
- Examination of HMMR overexpression in immortalized cancer cells.
- Investigating the PLK1-dependent pathway affecting Ran localization and NuMA-dynein complex modulation.
Main Results:
- Hmmr-knockout mice exhibit neonatal lethality, defective neural development, and multi-tissue phenotypes.
- HMMR acts at centrosomes in a PLK1-dependent manner to locate active Ran.
- HMMR modulates cortical NuMA-dynein complex localization, correcting mispositioned spindles.
Conclusions:
- HMMR is essential for the PLK1-dependent pathway that orients progenitor cell division.
- HMMR plays a critical role in supporting proper neural development.
- Dysregulation of HMMR impacts spindle orientation and may contribute to developmental defects.
Keywords:
asymmetric cell divisioncell biologydevelopmental biologyhumanmouseneurogenesisspindle orientationstem cellsMore Related Videos
Related Concept Videos
01:09Cytoskeletal Linker Proteins - Plakins
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
01:42Microtubule Associated Proteins (MAPs)
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
02:50Spindle Assembly
Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a microtubule array...
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a microtubule array...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...