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EVA-1 Functions as an UNC-40 Co-receptor to Enhance Attraction to the MADD-4 Guidance Cue in


During animal development, cells and cell extensions migrate along stereotypical paths to their target destination by interacting with guidance cues in their environment. The guidance receptors on the surface of these cells can each interact with several different cues, and many of the cues can each interact with multiple receptors. How a migrating cell can reach its target amid this apparent receptor-cue promiscuity is poorly understood. Here, we extend our earlier investigation of how the UNC-40 receptor, which is known to interact with the UNC-6 guidance cue, mediates attraction towards the MADD-4 guidance cue. We show that another transmembrane protein called EVA-1 increases the sensitivity of UNC-40 to MADD-4. This increase in sensitivity allows UNC-40 to respond to MADD-4 in the presence of UNC-6. Without EVA-1, UNC-6 dominates UNC-40 function and restricts its response to MADD-4. Hence, the presence of EVA-1 acts like a switch to change UNC-40's sensitivity from UNC-6 to MADD-4, and in turn allows UNC-40-expressing cells to migrate towards the source of MADD-4 within a field of the UNC-6 guidance cue.


Vyšlo v časopise: EVA-1 Functions as an UNC-40 Co-receptor to Enhance Attraction to the MADD-4 Guidance Cue in. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004521
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004521

Souhrn

During animal development, cells and cell extensions migrate along stereotypical paths to their target destination by interacting with guidance cues in their environment. The guidance receptors on the surface of these cells can each interact with several different cues, and many of the cues can each interact with multiple receptors. How a migrating cell can reach its target amid this apparent receptor-cue promiscuity is poorly understood. Here, we extend our earlier investigation of how the UNC-40 receptor, which is known to interact with the UNC-6 guidance cue, mediates attraction towards the MADD-4 guidance cue. We show that another transmembrane protein called EVA-1 increases the sensitivity of UNC-40 to MADD-4. This increase in sensitivity allows UNC-40 to respond to MADD-4 in the presence of UNC-6. Without EVA-1, UNC-6 dominates UNC-40 function and restricts its response to MADD-4. Hence, the presence of EVA-1 acts like a switch to change UNC-40's sensitivity from UNC-6 to MADD-4, and in turn allows UNC-40-expressing cells to migrate towards the source of MADD-4 within a field of the UNC-6 guidance cue.


Zdroje

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Genetika Reprodukčná medicína

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PLOS Genetics


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