The retinitis pigmentosa 1 protein is a photoreceptor microtubule-associated protein.

Abstract

The outer segments of rod and cone photoreceptor cells are highly specialized sensory cilia made up of hundreds of membrane discs stacked into an orderly array along the photoreceptor axoneme. It is not known how the alignment of the outer segment discs is controlled, although it has been suggested that the axoneme may play a role in this process. Mutations in the retinitis pigmentosa 1 (RP1) gene are a common cause of retinitis pigmentosa (RP). Disruption of the Rp1 gene in mice causes misorientation of outer segment discs, suggesting a role for RP1 in outer segment organization. Here, we show that the RP1 protein is part of the photoreceptor axoneme. Amino acids 28-228 of RP1, which share limited homology with the microtubule-binding domains of the neuronal microtubule-associated protein (MAP) doublecortin, mediate the interaction between RP1 and microtubules, indicating that the putative doublecortin (DCX) domains in RP1 are functional. The N-terminal portion of RP1 stimulates the formation of microtubules in vitro and stabilizes cytoplasmic microtubules in heterologous cells. Evaluation of photoreceptor axonemes from mice with targeted disruptions of the Rp1 gene shows that Rp1 proteins that contain the DCX domains also help control axoneme length and stability in vivo. These results demonstrate that RP1 is a MAP. Given the specific expression of RP1 in photoreceptors, RP1 is thus the first photoreceptor-specific MAP to be identified. Furthermore, these findings indicate that the RP1 form of inherited retinal degeneration is part of the larger class of neurodegenerative diseases caused by MAP dysfunction.

• Authors: Qin Liu, Jian Zuo, Eric A Pierce
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 24 Issue 29 Pg. 6427-36 (Jul 21 2004) ISSN: 1529-2401 [Electronic] United States
• PMID: 15269252 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dcx protein, mouse
• Doublecortin Protein
• Eye Proteins
• Microtubule-Associated Proteins
• RP1 protein, human
• RP1 protein, mouse

Topics

• Animals
• COS Cells
• Chlorocebus aethiops
• Doublecortin Protein
• Eye Proteins (analysis, genetics, physiology)
• Mice
• Mice, Mutant Strains
• Microtubule-Associated Proteins (analysis, genetics, physiology)
• Microtubules (chemistry, metabolism, ultrastructure)
• Photoreceptor Cells, Vertebrate (chemistry)
• Protein Structure, Tertiary