DLK-1/p38 MAP Kinase Signaling Controls Cilium Length by Regulating RAB-5 Mediated Endocytosis in Caenorhabditis elegans
| Autor: | Suzanne Rademakers, Aniek van der Vaart, Gert Jansen |
|---|---|
| Přispěvatelé: | Cell biology |
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
lcsh:QH426-470 MAP Kinase Signaling System GTP-Binding Protein alpha Subunits Gi-Go Biology Endocytosis Clathrin Motor protein Intraflagellar transport Genetics Animals Guanine Nucleotide Exchange Factors Cilia Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Genetics (clinical) Ecology Evolution Behavior and Systematics MAP kinase kinase kinase Cilium fungi MAP Kinase Kinase Kinases Transport protein Cell biology lcsh:Genetics biology.protein sense organs Rab Mitogen-Activated Protein Kinases Research Article |
| Zdroj: | PLoS Genetics (online), 11(12). Public Library of Science PLoS Genetics, Vol 11, Iss 12, p e1005733 (2015) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Cilia are sensory organelles present on almost all vertebrate cells. Cilium length is constant, but varies between cell types, indicating that cilium length is regulated. How this is achieved is unclear, but protein transport in cilia (intraflagellar transport, IFT) plays an important role. Several studies indicate that cilium length and function can be modulated by environmental cues. As a model, we study a C. elegans mutant that carries a dominant active G protein α subunit (gpa-3QL), resulting in altered IFT and short cilia. In a screen for suppressors of the gpa-3QL short cilium phenotype, we identified uev-3, which encodes an E2 ubiquitin-conjugating enzyme variant that acts in a MAP kinase pathway. Mutation of two other components of this pathway, dual leucine zipper-bearing MAPKKK DLK-1 and p38 MAPK PMK-3, also suppress the gpa-3QL short cilium phenotype. However, this suppression seems not to be caused by changes in IFT. The DLK-1/p38 pathway regulates several processes, including microtubule stability and endocytosis. We found that reducing endocytosis by mutating rabx-5 or rme-6, RAB-5 GEFs, or the clathrin heavy chain, suppresses gpa-3QL. In addition, gpa-3QL animals showed reduced levels of two GFP-tagged proteins involved in endocytosis, RAB-5 and DPY-23, whereas pmk-3 mutant animals showed accumulation of GFP-tagged RAB-5. Together our results reveal a new role for the DLK-1/p38 MAPK pathway in control of cilium length by regulating RAB-5 mediated endocytosis. Author Summary Cells detect cues in their environment using many different receptor and channel proteins, most of which localize to the plasma membrane of the cell. Some of these receptors and channels localize to a specialized sensory organelle, the primary cilium, that extends from the cell like a small antenna. Almost all cells of the human body have one or more cilia. Defects in cilium structure or function have been implicated in many diseases. Many studies have shown that the length of cilia is regulated and can be modulated by environmental signals. Several genes have been identified that function in cilium length regulation and it is clear that transport of proteins inside the cilium plays an important role. Here, we identify several genes of a MAP kinase cascade that modulate the length of cilia of the nematode Caenorhabditis elegans. Interestingly, this regulation seems not to be mediated by the transport system in the cilia, but by modulation of endocytosis. Our results suggest that regulated delivery and removal of proteins and/or lipids at the base of the cilium contributes to the regulation of cilium length. |
| Databáze: | OpenAIRE |
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