Cytoplasmic Cl- couples membrane remodeling to epithelial morphogenesis.
Proc Natl Acad Sci U S A
; 114(52): E11161-E11169, 2017 12 26.
Article
em En
| MEDLINE
| ID: mdl-29229864
ABSTRACT
Chloride is the major free anion in the extracellular space (>100 mM) and within the cytoplasm in eukaryotes (10 â¼ 20 mM). Cytoplasmic Cl- level is dynamically regulated by Cl- channels and transporters. It is well established that movement of Cl- across the cell membrane is coupled with cell excitability through changes in membrane potential and with water secretion. However, whether cytoplasmic Cl- plays additional roles in animal development and tissue homeostasis is unknown. Here we use genetics, cell biological and pharmacological tools to demonstrate that TMEM16A, an evolutionarily conserved calcium-activated chloride channel (CaCC), regulates cytoplasmic Cl- homeostasis and promotes plasma membrane remodeling required for mammalian epithelial morphogenesis. We demonstrate that TMEM16A-mediated control of cytoplasmic Cl- regulates the organization of the major phosphoinositide species PtdIns(4,5)P2 into microdomains on the plasma membrane, analogous to processes that cluster soluble and membrane proteins into phase-separated droplets. We further show that an adequate cytoplasmic Cl- level is required for proper endocytic trafficking and membrane supply during early stages of ciliogenesis and adherens junction remodeling. Our study thus uncovers a critical function of CaCC-mediated cytoplasmic Cl- homeostasis in controlling the organization of PtdIns(4,5)P2 microdomains and membrane remodeling. This newly defined role of cytoplasmic Cl- may shed light on the mechanisms of intracellular Cl- signaling events crucial for regulating tissue architecture and organelle biogenesis during animal development.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Membrana Celular
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Cloretos
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Fosfatidilinositol 4,5-Difosfato
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Anoctamina-1
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Morfogênese
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article