SARA-regulated vesicular targeting underlies formation of the light-sensing organelle in mammalian rods.
The light-sensing organelle of the vertebrate rod photoreceptor, the outer segment (OS), is a modified cilium containing approximately 1,000 stacked disc membranes that are densely packed with visual pigment rhodopsin. The mammalian OS is renewed every ten days; new discs are assembled at the base of the OS by a poorly understood mechanism. Our results suggest that discs are formed and matured in a process that involves specific phospholipid-directed vesicular membrane targeting. Rhodopsin-laden vesicles in the OS axonemal cytoplasm fuse with nascent discs that are highly specialized with abundant phosphatidylinositol 3-phosphate (PI3P). This membrane coupling is regulated by the FYVE domain-containing protein, SARA, through its direct interaction with PI3P, rhodopsin, and SNARE protein syntaxin 3. Our model, in contrast to the previously proposed evagination model, suggests that the vesicular delivery of rhodopsin in the OS concentrates rhodopsin into discs, and this process directly participates in disc biogenesis.
Chuang
Jen-Zen
JZ
Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. izchuang@med.cornell.edu
Zhao
Yu
Y
Sung
Ching-Hwa
CH
D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008027:Light; D051379:Mice; D015388:Organelles / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D012243:Rhodopsin / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000166:cytology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D012243:Rhodopsin; C116420:ZFYVE16 protein, human; D012697:Serine Endopeptidases
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