Phospholipase C83 is a novel binding partner of myosin VI and functions as anchoring of myosin VI on plasma membrane

摘要

Phosphoinositide metabolism contributes an important intracellular signaling system that is involved in a variety of cell functions such as hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking, ion channel activity, cytokinesis and regulation of the cytoskeleton (Di Paolo and De Camilli, 2006; Clapham, 2003; Janetopoulos and Devreotes, 2006; Fukami etal., 1992). Phospholipase C (PLC) (PI-PLC; E.C.3.1.4.11) is a key enzyme in this system and acts by hydrolyzing phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 s messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. Diacylglycerol mediates the activation of protein kinase C (E.C.2.7.1.37), and IP3 releases Ca~(2+) from intracellular stores (Nishizuka, 1988; Berridge and Irvine, 1984). Thirteen mammalian PLC isozymes have been identified so far, and they are divided into six classes, p (1-4)-, y (1, 2)-, 8 (1, 3,4)-, ?(1)-, ? (1)-, ti (1, 2)-type on the basis of structure and activation mechanisms (Suh et al., 2008; Fukami et al., 2010). Among these classes PLC8 is evolutionarily conserved from yeasts to mammals, and therefore, it is expected to have basic physiological functions. The PLCS class consists of three isozymes, namely, PLC81,83, and 84 (Irino et al., 2004). To understand the physiological functions of these PLCS isozymes, we have generated PLCS knockout mice and analyzed their phenotypes. We previously reported that PLC81 is necessary for skin homeostasis (Nakamura et al., 2003, 2008; Ichinohe et al., 2007) and that PLCS4 plays an essential role in the acrosome reaction of sperm (Fukami et al., 2001, 2003). However, PLC53KO mice show no obvious abnormality.