Membrane Targeting of C2GAP1 Enables Dictyostelium discoideum to Sense Chemoattractant Gradient at a Higher Concentration Range

Autor: Arjan Kortholt, Taeck J. Jeon, Smit Bhimani, Xi Wen, Henderikus Pots, Tian Jin, Xuehua Xu
Přispěvatelé: Cell Biochemistry
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Cell and Developmental Biology
Frontiers in Cell and Developmental Biology, 9:725073. Frontiers Media S.A.
Frontiers in Cell and Developmental Biology, Vol 9 (2021)
ISSN: 2296-634X
Popis: Chemotaxis, which is G protein-coupled receptor (GPCR)-mediated directional cell migration, plays pivotal roles in diverse human diseases, including recruitment of leukocytes to inflammation sites and metastasis of cancer. It is still not fully understood how eukaryotes sense and chemotax in response to chemoattractants with an enormous concentration range. A genetically traceable model organism, Dictyostelium discoideum, is the best-studied organism for GPCR-mediated chemotaxis. Recently, we have shown that C2GAP1 controls G protein coupled receptor-mediated Ras adaptation and chemotaxis. Here, we investigated the molecular mechanism and the biological function of C2GAP1 membrane targeting for chemotaxis. We show that calcium and phospholipids on the plasma membrane play critical roles in membrane targeting of C2GAP1. Cells lacking C2GAP1 (c2gapA–) displayed an improved chemotaxis in response to chemoattractant gradients at subsensitive or low concentrations (1 μM). Taken together, our results demonstrate that the membrane targeting of C2GAP1 enables Dictyostelium to sense chemoattractant gradients at a higher concentration range. This mechanism is likely an evolutionarily conserved molecular mechanism of Ras regulation in the adaptation and chemotaxis of eukaryotes.
Databáze: OpenAIRE