title: The Cytoskeletal Connection to Ion Channels as a Potential Mechanosensory Mechanism: Lessons from Polycystin-2 (TRPP2).
abstract: Mechanosensitivity of ion channels, or the ability to transfer mechanical forces into a gating mechanism of channel regulation, is split into two main working (not mutually exclusive) hypotheses. One is that elastic and/or structural changes in membrane properties act as a transducing mechanism of channel regulation. The other hypothesis involves tertiary elements, such as the cytoskeleton which, itself by dynamic interactions with the ion channel, may convey conformational changes, including those ascribed to mechanical forces. This hypothesis is supported by numerous instances of regulatory changes in channel behavior by alterations in cytoskeletal structures/interactions. However, only recently, the molecular nature of these interactions has slowly emerged. Recently, a surge of evidence has emerged to indicate that transient receptor potential (TRP) channels are key elements in the transduction of a variety of environmental signals. This chapter describes the molecular linkage and regulatory elements of polycystin-2 (PC2), a TRP-type (TRPP2) nonselective cation channel whose mutations cause autosomal dominant polycystic kidney disease (ADPKD). The chapter focuses on the involvement of cytoskeletal structures in the regulation of PC2 and discusses how these connections are the transducing mechanism of environmental signals to its channel function.
authors.affiliation: Renal Unit, Massachusetts General Hospital East, Charlestown, Massachusetts 02129; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115; Laboratorio de Canales Iónicos, Departamento de Fisicoquímica y Química Analítica, Facultad de Farmacia y Bioquímica, Buenos Aires 1113, Argentina.
authors.forename: Horacio F
authors.initials: HF
authors.lastname: Cantiello
authors.affiliation: Laboratorio de Canales Iónicos, Departamento de Fisicoquímica y Química Analítica, Facultad de Farmacia y Bioquímica, Buenos Aires 1113, Argentina.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Montalbetti
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada.
authors.forename: Xing-Zhen
authors.initials: XZ
authors.lastname: Chen