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Usher Syndrome Protein Network Functions in the Retina and their Relation to Other Retinal Ciliopathies

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically and clinically heterogeneous: 15 chromosomal loci assigned to 3 clinical types, USH1-3. All USH1 and 2 proteins are organized into protein networks by the scaffold proteins harmonin (USH1C), whirlin (USH2D) and SANS (USH1G). This has contributed essentially to our current understanding of the USH protein function in the eye and the ear and explains why defects in proteins of different families cause very similar phenotypes. Ongoing in depth analyses of USH protein networks in the eye indicated cytoskeletal functions as well as roles in molecular transport processes and ciliary cargo delivery in photoreceptor cells. The analysis of USH protein networks revealed molecular links of USH to other ciliopathies, including non-syndromic inner ear defects and isolated retinal dystrophies but also to kidney diseases and syndromes like the Bardet-Biedl syndrome. These findings provide emerging evidence that USH is a ciliopathy molecularly related to other ciliopathies, which opens an avenue for common therapy strategies to treat these diseases.

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Abbreviations

Ax:

Axoneme

BB:

Basal body

BBS:

Bardet-Biedl syndrome

CC:

Connecting cilium

Cdh 23:

Cadherin 23

Cep290:

Centrosomal protein of 290 kDa

CP:

Calycal processes

Gpr98:

G protein-coupled receptor 98

IFT:

Intraflagellar transport

IS:

Inner segment

LCA:

Leber congenital amaurosis

MKS:

Meckel-Gruber syndrome

NPHP:

Nephronophthisis

Nlp:

Ninein-like protein

NlpisoB :

Ninein-like protein isoform B

OLM:

Outer limiting membrane

OS:

Outer segment

P:

Perikaryon

PMC:

Periciliary membrane complex

Pcdh15:

Protocadherin 15

RP:

Retinitis pigmentosa

RPE:

Retinal pigment epithelium

RPGR:

RP GTPase regulator

RPGRIP1:

RPGR interacting protein 1

S:

Synapse

SANS:

Scaffold protein containg ankyrin repeats and SAM domain

SLS:

Senior-Loken syndrome

Tz:

Transition zone

USH:

Human Usher syndrome

VLGR1:

Very large G-protein coupled receptor protein 1

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Supports

DFG; EU FP7 “SYSCILIA” and “TREATRUSH”; FAUN-Stiftung; Foundation Fighting Blindness (FFB); Forschung contra Blindheit; ProRetina Deutschland.

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Authors and Affiliations

  1. Institute of Zoology, Dept. Cell & Matrix Biology, Johannes Gutenberg University Mainz, Mainz, Germany

    Nasrin Sorusch, Kirsten Wunderlich, Katharina Bauss, Kerstin Nagel-Wolfrum & Uwe Wolfrum

Authors
  1. Nasrin Sorusch
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  2. Kirsten Wunderlich
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  3. Katharina Bauss
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  4. Kerstin Nagel-Wolfrum
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  5. Uwe Wolfrum
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Corresponding author

Correspondence to Uwe Wolfrum .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

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Sorusch, N., Wunderlich, K., Bauss, K., Nagel-Wolfrum, K., Wolfrum, U. (2014). Usher Syndrome Protein Network Functions in the Retina and their Relation to Other Retinal Ciliopathies. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_67

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_67

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

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