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Multiprotein Complexes of Retinitis Pigmentosa GTPase Regulator (RPGR), a Ciliary Protein Mutated in X-Linked Retinitis Pigmentosa (XLRP)

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Book cover Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 664))

Abstract

Mutations in Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of X-linked Retinitis Pigmentosa (XLRP). The RPGR gene undergoes extensive alternative splicing and encodes for distinct protein isoforms in the retina. Extensive studies using isoform-specific antibodies and mouse mutants have revealed that RPGR predominantly localizes to the transition zone to primary cilia and associates with selected ciliary and microtubule-associated assemblies in photoreceptors. In this chapter, we have summarized recent advances on understanding the role of RPGR in photoreceptor protein trafficking. We also provide new evidence that suggests the existence of discrete RPGR multiprotein complexes in photoreceptors. Piecing together the RPGR-interactome in different subcellular compartments should provide critical insights into the role of alternative RPGR isoforms in associated orphan and syndromic retinal degenerative diseases.

Retinitis Pigmentosa (RP: MIM #268000) is a leading cause of inherited blindness in developed countries. RP refers to a group of debilitating neurodegenerative diseases with clinically heterogeneous findings, which include bone spicule like pigmentary deposits in the retina, progressive loss of peripheral vision and eventually deterioration of central vision due to cone loss (Bird 1987; Fishman et al. 1988; Heckenlively et al. 1988; Sullivan and Daiger 1996). Over 30 RP genes have been identified so far (http://www.sph.uth.tmc.edu/Retnet) (Hartong et al. 2006). No effective approach exists for the management or treatment of RP.

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Acknowledgments

This work is supported by the grants from the National Eye Institute (RO1-EY007961), Midwest Eye Banks and Transplantation Center, and by NEI/NIH intramural program.

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Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, Ann Arbor, MI, 48105, USA

    Carlos Murga-Zamalloa & Hemant Khanna

  2. Neurobiology-Neurodegeneration and Repair laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Anand Swaroop

Authors
  1. Carlos Murga-Zamalloa
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  2. Anand Swaroop
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  3. Hemant Khanna
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Correspondence to Hemant Khanna .

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Editors and Affiliations

  1. Health Science Center, University of Oklahoma, Stanton L. Young Blvd. 608, Oklahoma City, 73104, USA

    Robert E. Anderson

  2. Division of Ophthalmology, Cleveland Clinic Foundation, Euclid Ave. 9500, Cleveland, 44195, USA

    Joe G. Hollyfield

  3. School of Medicine, University of California, San Francisco, Kirkham St. 10, San Francisco, 94143, USA

    Matthew M. LaVail

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Murga-Zamalloa, C., Swaroop, A., Khanna, H. (2010). Multiprotein Complexes of Retinitis Pigmentosa GTPase Regulator (RPGR), a Ciliary Protein Mutated in X-Linked Retinitis Pigmentosa (XLRP). In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_13

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