Tetraspanin CD 81 is required for the v 5 - integrin - dependent particle - binding step of RPE phagocytosis

Introduction The retinal pigment epithelium (RPE) forms the outermost layer of the retina and consists of simple, cuboidal epithelial cells with unique plasma membrane polarity (Marmorstein, 2001). In the mammalian retina, each RPE cell underlies ~30 photoreceptor neurons all of which shed the aged, distal tip of their outer segment every morning stimulated by light and circadian rhythms (Young, 1967). RPE cells promptly and efficiently recognize and engulf shed photoreceptor outer segment fragments (POS) by receptor-mediated phagocytosis (Young and Bok, 1969). Thus, an individual post-mitotic RPE cell disposes of several thousand outer segment membrane disks once a day for decades. Synchronized RPE phagocytosis is critical for vision since its deficiency causes blindness in The molecular mechanism used by RPE cells to phagocytose POS belongs to a group of non-inflammatory clearance mechanisms used by other cell types to phagocytose apoptotic cells (Finnemann and Rodriguez-Boulan, 1999; Scott et al., 2001). These uptake pathways employ the integrin adhesion receptors ␣v␤3/␣v␤5, Mer tyrosine kinase (MerTK; also known as Mertk or Mer) and the scavenger receptor CD36 (reviewed by Wu et al., 2006). ␣v␤5 is the sole apical integrin receptor of the RPE in the mammalian eye and the only surface receptor shown thus far to be essential for POS binding by RPE cells (Finnemann et al., 1997; Nandrot et al., 2004). Furthermore, POS recognition by ␣v␤5 integrin activates a signaling pathway involving focal