Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice

Sahly, Iman; Dufour, Éric; Schietroma, Cataldo; Michel, Vincent; Bahloul, Amel; Perfettini, Isabelle; Pepermans, Elise; Estivalet, Amrit; Carette, Diane; Aghaie, Asadollah; Ebermann, Inga; Lelli, Andrea; Iribarne, María; Hardelin, Jean‐Pierre; Weil, Dominique; Sahel, José‐Alain; El-Amraoui, Aziz; Petit, Christine

doi:10.1083/jcb.201202012

Cited by 159 publications

(292 citation statements)

References 77 publications

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“…The binding partner of PCDH21 on the IS remains to be identified. It is not clear whether or not PCDH15 is on the IS (38,39), but members of the USH1 network, which include PCDH15 and CDH23, are possible candidates. The presence of cadherin-containing links between the tips of the nascent discs and the IS provides significant further evidence the discs are plasma membrane evaginations, rather than cytoplasmic vesicles, corroborating the evagination model rather than the fusion model.…”

Section: Discussionmentioning

confidence: 99%

Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment

Burgoyne

Meschede

Burden

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

100

103

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The outer segments of vertebrate rod photoreceptors are renewed every 10 d. Outer segment components are transported from the site of synthesis in the inner segment through the connecting cilium, followed by assembly of the highly ordered discs. Two models of assembly of discrete discs involving either successive fusion events between intracellular rhodopsin-bearing vesicles or the evagination of the plasma membrane followed by fusion of adjacent evaginations have been proposed. Here we use immuno-electron microscopy and electron tomography to show that rhodopsin is transported from the inner to the outer segment via the ciliary plasma membrane, subsequently forming successive evaginations that "zipper" up proximally, but at their leading edges are free to make junctions containing the protocadherin, PCDH21, with the inner segment plasma membrane. Given the physical dimensions of the evaginations, coupled with likely instability of the membrane cortex at the distal end of the connecting cilium, we propose that the evagination occurs via a process akin to blebbing and is not driven by actin polymerization. Disassembly of these junctions is accompanied by fusion of the leading edges of successive evaginations to form discrete discs. This fusion is topologically different to that mediated by the membrane fusion proteins, SNAREs, as initial fusion is between exoplasmic leaflets, and is accompanied by gain of the tetraspanin rim protein, peripherin.rod photoreceptors | disc renewal | rhodopsin | protocadherin R od photoreceptors are specialized neurons of the vertebrate retina responsible for vision in dim light. The cylindrical outer segment (OS) contains ∼1,000 stacked discontinuous membranous discs packed with the light-sensitive pigment rhodopsin. This contrasts with the cone OS, which consists of a series of evaginations of the plasma membrane that remain exposed to the extracellular space (1). OS constituents are synthesized in the inner segment (IS) and then transported to the OS via a nonmotile cilium (connecting cilium) that resembles the transition zone of the primary cilium. Because of the high metabolic demand of phototransduction, OS discs undergo daily renewal, whereby the tip (distal end) is shed and phagocytosed by the retinal pigment epithelium while new discs are formed at the base (proximal end) of the OS (2, 3). How these discs are generated and rhodopsin incorporated remains controversial. The evagination model proposes that the ciliary plasma membrane evaginates to form discs that are initially exposed to the extracellular space and then pinch off to form fully closed discs (4). In contrast, the fusion model proposes that discs originate from rhodopsincontaining vesicles, which undergo homotypic fusion to form new discs (5, 6). Conventional electron microscopic (EM) analyses of chemically fixed specimens have clearly shown discs open to the extracellular space at the base of the OS, supporting the evagination model (4,7,8). Furthermore, studies in amphibians have demonstrated that membrane imper...

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Section: Discussionmentioning

confidence: 99%

Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment

Burgoyne

Meschede

Burden

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

100

103

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“…Mouse knockouts of the USH1 proteins (myosin VIIa, harmonin, cadherin-23, protocadherin-15, SANS) often develop hearing loss and vestibular dysfunction but do not display retinal degeneration due to the lack of CPs. 20 Amphibians (especially Xenopus tadpoles) or macaques are a better model of USH1 as they possess CPs, but zebrafish are more commonly used for most models of Usher syndrome.…”

Section: Model Systems For the Study Of Photoreceptor Development Andmentioning

confidence: 99%

The role of primary cilia in the development and disease of the retina

2013

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“…Both isoforms are localized to actin bundle-based structures in sensory cells, including the calycal process of photoreceptors (2,6,7) and the stereocilia of inner ear hair cells (8). MYO3A and -3B are proposed to play a role in maintaining the length of the actin-bundled structures (9,10).…”

mentioning

confidence: 99%

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop

Quintero

Unrath

Stevens

et al. 2013

Journal of Biological Chemistry

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Background: Class III myosins contain both a motor and kinase domain. Results: Phosphorylation of the kinase activation loop enhances MYO3A kinase activity, augmenting autophosphorylationinduced attenuation of motor and cellular activity. Conclusion: MYO3A kinase activity mediates localization and function within actin protrusions. Significance: Characterizing MYO3A kinase regulation enhances our understanding of the role of MYO3A in the maintenance of actin protrusions found in sensory epithelia.

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Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice

Abstract: Mice are a poor model for retinal defects caused by type I Usher syndrome (USH1) because their photoreceptors have almost no calyceal processes, the structures in which all USH1 proteins are detected in other vertebrates.

Cited by 159 publications

References 77 publications

Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment

Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment

The role of primary cilia in the development and disease of the retina

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop

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