May 2004
Volume 45, Issue 13
ARVO Annual Meeting Abstract  |   May 2004
RP1 is a photoreceptor–specific microtubule–associated protein
Author Affiliations & Notes
  • Q. Liu
    F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA
  • E.A. Pierce
    F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA
  • RP1 Consortium
    F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships  Q. Liu, None; E.A. Pierce, None.
  • Footnotes
    Support  NIH (EY12910), FFB, RPB, Rosanne Silbermann Foundation
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 2439. doi:
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      Q. Liu, E.A. Pierce, RP1 Consortium; RP1 is a photoreceptor–specific microtubule–associated protein . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2439.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose: Mutations in RP1 are a common cause of dominant retinitis pigmentosa (RP). The photoreceptor–specific RP1 protein is located in the outer segment portion of the photoreceptor axoneme, and contains a region of homology (amino acids 28–228) to the microtubule binding domains of the neuron–specific microtubule–associated protein (MAP) doublecortin (DCX), suggesting that RP1 could be a MAP. To evaluate the possibility that RP1 is a MAP, we have investigated the ability of RP1 to modulate microtubule polymerization and stability. Methods: The ability of endogenous mouse Rp1 and recombinant human RP1 proteins to co–polymerize with microtubules was assessed using standard centrifugation techniques. The locations of recombinant RP1 proteins containing different portions of RP1 in COS–7 cells were evaluated by co–immunostaining transfected cells with antibodies to the RP1 proteins and α–tubulin. The ability of two recombinant RP1 proteins, N1–RP1 (codons 1–682) and N2–RP1 (codons 238–682), to stimulate tubulin polymerization was tested in vitro. The stability of the cytoplasmic microtubules in N1–RP1 and N2–RP1 transfected COS–7 cells was assessed using the microtubule depolymerizing agent nocodazole. Results: Endogenous Rp1 in mouse retina and recombinant N1–RP1 protein produced in transfected cells bound to and co–sedimented with microtubules. The N1–RP1 recombinant protein, which contains the DCX domains, demonstrated MAP activities. It stabilized the cytoplasmic microtubule network in transfected COS–7 cells, and greatly enhanced the rate and extent of tubulin polymerization in vitro. In contrast, the N2–RP1 recombinant protein, and other RP1 proteins which lack the DCX domains, lost the ability to bind to microtubules. Similarly, the N2–RP1 protein did not stablize cytoplasmic microtubule networks or to stimulate tubulin polymerization. Conclusions: RP1 co–assembles with microtubules from retina. The N–terminal 1/3 of RP1 stimulates the assembly of tubulin into microtubules, and stabilizes existing microtubules. These data demonstrate that the DCX domains in RP1 are active, and RP1 is a MAP. RP1 is thus the first photoreceptor–specific MAP identified. In addition, these findings place the RP1 form of RP in the group of neurodegenerative disorders caused by dysfunction of MAPs, and provide insight into the role of RP1 in photoreceptor outer segment biology.

Keywords: photoreceptors • cytoskeleton • protein structure/function 

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