TGFβ receptor endocytosis and Smad signaling require synaptojanin1, PI3K-C2α-, and INPP4B-mediated phosphoinositide conversions.

ABSTRACT: Phosphoinositide conversion regulates a diverse array of dynamic membrane events including endocytosis. However, it is not well understood which enzymes are involved in phosphoinositide conversions for receptor endocytosis. We found by small interfering RNA (siRNA)-mediated knockdown (KD) that class II PI3K α-isoform (PI3K-C2α), the 5'-phosphatase synaptojanin1 (Synj1), and the 4'-phosphatase INPP4B, but not PI3K-C2β, Synj2, or INPP4A, were required for TGFβ-induced endocytosis of TGFβ receptor. TGFβ induced rapid decreases in PI(4,5)P₂ at the plasma membrane (PM) with increases in PI(4)P, followed by increases in PI(3,4)P₂, in a TGFβ receptor kinase ALK5-dependent manner. TGFβ induced the recruitment of both synaptojanin1 and PI3K-C2α to the PM with their substantial

SUBMITTER: Aki S 

PROVIDER: S-EPMC7183790 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature