Abstract
Endosomal trafficking of receptors and associated proteins plays a critical role in signal processing. Until recently, it was thought that trafficking was shut down during cell division. Thus, remarkably, the regulation of trafficking during division remains poorly characterized. Here we delineate the role of mitotic kinases in receptor trafficking during asymmetric division. Targeted perturbations reveal that Cyclin-dependent Kinase 1 (CDK1) and Aurora Kinase promote storage of Fibroblast Growth Factor Receptors (FGFRs) by suppressing endosomal degradation and recycling pathways. As cells progress through metaphase, loss of CDK1 activity permits differential degradation and targeted recycling of stored receptors, leading to asymmetric induction. Mitotic receptor storage, as delineated in this study, may facilitate rapid reestablishment of signaling competence in nascent daughter cells. However, mutations that limit or enhance the release of stored signaling components could alter daughter cell fate or behavior thereby promoting oncogenesis.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Animals
-
Animals, Genetically Modified
-
Aurora Kinases / genetics
-
Aurora Kinases / physiology*
-
CDC2 Protein Kinase / genetics
-
CDC2 Protein Kinase / physiology*
-
Cell Cycle Proteins / metabolism
-
Ciona intestinalis / embryology
-
Ciona intestinalis / genetics
-
Embryo, Nonmammalian
-
Mitosis / genetics
-
Mitosis / physiology*
-
Protein Transport / genetics
-
Receptors, Fibroblast Growth Factor / genetics
-
Receptors, Fibroblast Growth Factor / metabolism*
-
Receptors, Growth Factor / genetics
-
Receptors, Growth Factor / metabolism
-
Signal Transduction / genetics
-
Tissue Distribution / genetics
Substances
-
Cell Cycle Proteins
-
Receptors, Fibroblast Growth Factor
-
Receptors, Growth Factor
-
Aurora Kinases
-
CDC2 Protein Kinase
Grants and funding
C.D.C. was supported by her American Heart Association Postdoctoral Award (16POST27250075). All authors were supported by the National Science Foundation (NSF) (grant #1656571 awarded to B.D.) Some of the student’s summer salaries along with purchase of some of their research supplies were funded by Swarthmore College. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.