The progressive rod–cone degeneration (PRCD) protein is secreted through the conventional ER/Golgi-dependent pathway

Remez, Lital; Zobor, Ditta; Kohl, Susanne; Ben-Yosef, Tamar

doi:10.1016/j.exer.2014.06.017

Cited by 9 publications

(15 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tubby domain of TUB also interacted with PRCD (Figure 3a,b). We next used pull-down experiments to test the effect of the following missense mutations (detected in human patients) on PRCD-TULP1 interaction: PRCD: p.C2Y and p.P25T [9,22]; TULP1: p.R311Q, p.N349K, p.G368W, p.F382S, p.R400W, p.R420P, p.K489R, and p.F491L (all located within the tubby domain) [16,[23][24][25][26][27]]. An interaction between PRCD and TULP1 was observed for all tested mutations (Figure 4).…”

Section: Prcd's Interaction With Tulp1 and Tub Is Mediated By The Highly Conserved Tubby Domainmentioning

confidence: 99%

TULP1 and TUB Are Required for Specific Localization of PRCD to Photoreceptor Outer Segments

Remez

Cohen

Nevet

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Photoreceptor disc component (PRCD) is a small protein which is exclusively localized to photoreceptor outer segments, and is involved in the formation of photoreceptor outer segment discs. Mutations in PRCD are associated with retinal degeneration in humans, mice, and dogs. The purpose of this work was to identify PRCD-binding proteins in the retina. PRCD protein-protein interactions were identified when implementing the Ras recruitment system (RRS), a cytoplasmic-based yeast two-hybrid system, on a bovine retina cDNA library. An interaction between PRCD and tubby-like protein 1 (TULP1) was identified. Co-immunoprecipitation in transfected mammalian cells confirmed that PRCD interacts with TULP1, as well as with its homolog, TUB. These interactions were mediated by TULP1 and TUB highly conserved C-terminal tubby domain. PRCD localization was altered in the retinas of TULP1- and TUB-deficient mice. These results show that TULP1 and TUB, which are involved in the vesicular trafficking of several photoreceptor proteins from the inner segment to the outer segment, are also required for PRCD exclusive localization to photoreceptor outer segment discs.

show abstract

Section: Prcd's Interaction With Tulp1 and Tub Is Mediated By The Highly Conserved Tubby Domainmentioning

confidence: 99%

TULP1 and TUB Are Required for Specific Localization of PRCD to Photoreceptor Outer Segments

Remez

Cohen

Nevet

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…The disease is caused by a single C2Y mutation in the Prcd gene, which is expressed specifically in the retina (6,7). Since the gene's discovery, human patients diagnosed with retinitis pigmentosa have been identified with mutations in Prcd, including the same C2Y mutation (6,(8)(9)(10)(11)(12). In both human and canine patients, the disease is autosomal recessive and characterized by a relatively slow, progressive death of rod photoreceptors followed by cones (5,6).…”

mentioning

confidence: 99%

PRCD is essential for high-fidelity photoreceptor disc formation

Spencer

Ding

Lewis

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Progressive rod-cone degeneration (PRCD) is a small protein residing in the light-sensitive disc membranes of the photoreceptor outer segment. Until now, the function of PRCD has remained enigmatic despite multiple demonstrations that its mutations cause blindness in humans and dogs. Here, we generated a PRCD knockout mouse and observed a striking defect in disc morphogenesis, whereby newly forming discs do not properly flatten. This leads to the budding of disc-derived vesicles, specifically at the site of disc morphogenesis, which accumulate in the interphotoreceptor matrix. The defect in nascent disc flattening only minimally alters the photoreceptor outer segment architecture beyond the site of new disc formation and does not affect the abundance of outer segment proteins and the photoreceptor’s ability to generate responses to light. Interestingly, the retinal pigment epithelium, responsible for normal phagocytosis of shed outer segment material, lacks the capacity to clear the disc-derived vesicles. This deficiency is partially compensated by a unique pattern of microglial migration to the site of disc formation where they actively phagocytize vesicles. However, the microglial response is insufficient to prevent vesicular accumulation and photoreceptors of PRCD knockout mice undergo slow, progressive degeneration. Taken together, these data show that the function of PRCD is to keep evaginating membranes of new discs tightly apposed to each other, which is essential for the high fidelity of photoreceptor disc morphogenesis and photoreceptor survival.

show abstract

“…Consistent with this hypothesis, the C2Y PRCD mutant is found in much lower abundance than wild type PRCD when expressed in both electroporated rods and cell culture. 8 …”

Section: Discussionmentioning

confidence: 99%

“…The time course of this disease varies across both dog and human patients, but overall, is relatively slow when compared to other inherited retinal degenerations. 3, 8–11 …”

mentioning

confidence: 99%

Progressive Rod–Cone Degeneration (PRCD) Protein Requires N-Terminal S-Acylation and Rhodopsin Binding for Photoreceptor Outer Segment Localization and Maintaining Intracellular Stability

et al. 2016

View full text Add to dashboard Cite

The light-sensing outer segments of photoreceptor cells harbor hundreds of flattened membranous discs containing the visual pigment, rhodopsin, and all the proteins necessary for visual signal transduction. PRCD (Progressive Rod-Cone Degeneration) is one of a few proteins residing specifically in photoreceptor discs, and the only one with completely unknown function. The importance of PRCD is highlighted by its mutations causing photoreceptor degeneration and blindness in canine and human patients. Here we report that PRCD is S-acylated at its N-terminal cysteine and anchored to the cytosolic surface of disc membranes. We also showed that mutating the S-acylated cysteine to tyrosine, a common cause of blindness in dogs and found in affected human families, causes PRCD to be completely mislocalized from the photoreceptor outer segment. We next undertook a proteomic search for PRCD interacting partners in disc membranes and found that it binds rhodopsin. This interaction was confirmed by reciprocal precipitation and co-chromatography experiments. We further demonstrated this interaction to be critically important for supporting the intracellular stability of PRCD, as the knockout of rhodopsin caused a drastic reduction in the photoreceptor content of PRCD. These data reveal the cause of photoreceptor disease in PRCD mutant dogs, and implicate rhodopsin to be involved in PRCD’s unknown, yet essential function in photoreceptors.

show abstract

The progressive rod–cone degeneration (PRCD) protein is secreted through the conventional ER/Golgi-dependent pathway

Cited by 9 publications

References 30 publications

TULP1 and TUB Are Required for Specific Localization of PRCD to Photoreceptor Outer Segments

TULP1 and TUB Are Required for Specific Localization of PRCD to Photoreceptor Outer Segments

PRCD is essential for high-fidelity photoreceptor disc formation

Progressive Rod–Cone Degeneration (PRCD) Protein Requires N-Terminal S-Acylation and Rhodopsin Binding for Photoreceptor Outer Segment Localization and Maintaining Intracellular Stability

Contact Info

Product

Resources

About