A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells

Tina Maerker, Erwin van Wijk, Nora Overlack, Ferry F J Kersten, Joann Mcgee, Tobias Goldmann, Elisabeth Sehn, Ronald Roepman, Edward J. Walsh, Hannie Kremer, Uwe Wolfrum

Research output: Contribution to journalArticle

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Abstract

The human Usher syndrome (USH) is the most frequent cause of combined deaf-blindness. USH is genetically heterogeneous with at least 12 chromosomal loci assigned to three clinical types, USH1-3. Although these USH types exhibit similar phenotypes in human, the corresponding gene products belong to very different protein classes and families. The scaffold protein harmonin (USH1C) was shown to integrate all identified USH1 and USH2 molecules into protein networks. Here, we analyzed a protein network organized in the absence of harmonin by the scaffold proteins SANS (USH1G) and whirlin (USH2D). Immunoelectron microscopic analyses disclosed the colocalization of all network components in the apical inner segment collar and the ciliary apparatus of mammalian photoreceptor cells. In this complex, whirlin and SANS directly interact. Furthermore, SANS provides a linkage to the microtubule transport machinery, whereas whirlin may anchor USH2A isoform b and VLGR1b (very large G-protein coupled receptor 1b) via binding to their cytodomains at specific membrane domains. The long ectodomains of both transmembrane proteins extend into the gap between the adjacent membranes of the connecting cilium and the apical inner segment. Analyses of Vlgr1/del7TM mice revealed the ectodomain of VLGR1b as a component of fibrous links present in this gap. Comparative analyses of mouse and Xenopus photoreceptors demonstrated that this USH protein network is also part of the periciliary ridge complex in Xenopus. Since this structural specialization in amphibian photoreceptor cells defines a specialized membrane domain for docking and fusion of transport vesicles, we suggest a prominent role of the USH proteins in cargo shipment.

Original languageEnglish (US)
Pages (from-to)71-86
Number of pages16
JournalHuman Molecular Genetics
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2008

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Vertebrate Photoreceptor Cells
Usher Syndromes
Proteins
Photoreceptor Cells
G-Protein-Coupled Receptors
Xenopus
Membranes
Transport Vesicles
Cilia
Amphibians
Blindness
Microtubules
Protein Isoforms
Phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. / Maerker, Tina; van Wijk, Erwin; Overlack, Nora; Kersten, Ferry F J; Mcgee, Joann; Goldmann, Tobias; Sehn, Elisabeth; Roepman, Ronald; Walsh, Edward J.; Kremer, Hannie; Wolfrum, Uwe.

In: Human Molecular Genetics, Vol. 17, No. 1, 01.01.2008, p. 71-86.

Research output: Contribution to journalArticle

Maerker, T, van Wijk, E, Overlack, N, Kersten, FFJ, Mcgee, J, Goldmann, T, Sehn, E, Roepman, R, Walsh, EJ, Kremer, H & Wolfrum, U 2008, 'A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells', Human Molecular Genetics, vol. 17, no. 1, pp. 71-86. https://doi.org/10.1093/hmg/ddm285
Maerker, Tina ; van Wijk, Erwin ; Overlack, Nora ; Kersten, Ferry F J ; Mcgee, Joann ; Goldmann, Tobias ; Sehn, Elisabeth ; Roepman, Ronald ; Walsh, Edward J. ; Kremer, Hannie ; Wolfrum, Uwe. / A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. In: Human Molecular Genetics. 2008 ; Vol. 17, No. 1. pp. 71-86.
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