Channel-interacting PDZ protein “CIPP” interacts with proteins involved in cytoskeletal dynamics

Emanuele Alpi , Elena Landi , Manuela Barilari , Michela Serresi , Piero Salvadori , Angela Bachi , Luciana Dente (1)

1 Cell and Developmental Biology Laboratory, Department of Biology

Neuronal CIPP is a multivalent PDZ protein that interacts with specific channels and receptors, highly expressed in the brain. It is composed of four PDZ domains that behave as a scaffold to clusterize functionally connected proteins. In this study, we selected a set of potential CIPP interactors that are directly or indirectly involved in mechanisms of cytoskeletal remodeling and membrane protrusions formation. For some of these, we first proved the direct binding to specific CIPP PDZ domains considered as autonomous elements, and then confirmed the interaction with the whole protein. In particular, the small G-protein effector IRSp53 (insulin receptor tyrosine kinase substrate protein p53) specifically interacts with the second PDZ domain of CIPP and, when co-transfected in mammalian cultured cells with a tagged full-length CIPP, it induces a marked reorganization of CIPP cytoplasmic localization. Large punctate structures are generated as a consequence of CIPP binding to IRSp53 carboxy-terminus. Analysis of the puncta nature, using various endocytic markers, revealed that they are not related to cytoplasmic vesicles, rather represent multi-protein assemblies, where CIPP can tether other potential interactors.

Mots clés: Life Sciences

Emanuele Alpi, Elena Landi, Manuela Barilari, Michela Serresi, Piero Salvadori, et al.. Channel-interacting PDZ protein “CIPP” interacts with proteins involved in cytoskeletal dynamics. Biochemical Journal, 2009, 419 (2), pp.289-300. ⟨10.1042/BJ20081387⟩. ⟨hal-00479066⟩