Loss of the Cholesterol-Binding Protein Prominin-1/CD133 Causes Disk Dysmorphogenesis and Photoreceptor Degeneration

Abstract

Prominin-1/CD133 (Prom-1) is a commonly used marker of neuronal, vascular, hematopoietic and other stem cells, yet little is known about its biological role and importance in vivo. Here, we show that loss of Prom-1 results in progressive degeneration of mature photoreceptors with complete loss of vision. Despite the expression of Prom-1 on endothelial progenitors, photoreceptor degeneration was not attributable to retinal vessel defects, but caused by intrinsic photoreceptor defects in disk formation, outer segment morphogenesis, and associated with visual pigment sorting and phototransduction abnormalities. These findings shed novel insight on how Prom-1 regulates neural retinal development and phototransduction in vertebrates.

Accumulation of non-outer segment proteins in the outer segment underlies photoreceptor degeneration in Bardet–Biedl syndrome

“…6A, green arrowhead). This disk morphogenesis defect is similar to what was observed in Prom1 mutant photoreceptor cells, mutations of which cause progressive retinal degeneration in mammals (35)(36)(37). Therefore, although Prom1 showed only a moderate change in our quantitative proteomic study (∼50% reduction in Lztfl1 OSs compared with wild-type; Dataset S1), we examined localization of Prom1 in Lztfl1 and Bbs1 mutant retinas.…”

CD133 is a modifier of hematopoietic progenitor frequencies but is dispensable for the maintenance of mouse hematopoietic stem cells

“…The latter animals are viable and fertile but are affected with a retinal degeneration leading to blindness (26). No obvious hematopoietic defects were reported in CD133 KO mice, although this issue was not investigated vigorously (26). Here, we demonstrated that CD133 is indeed expressed by mouse HPCs but that HSC purification based on CD133 protein is not possible, suggesting a substantial species difference for the role of CD133 on HSCs.…”

“…In the present study, we have investigated the influence of CD133 in HSC maintenance and hematopoiesis using wild-type and CD133 knockout (KO) mice (26). The latter animals are viable and fertile but are affected with a retinal degeneration leading to blindness (26).…”

“…The latter animals are viable and fertile but are affected with a retinal degeneration leading to blindness (26). No obvious hematopoietic defects were reported in CD133 KO mice, although this issue was not investigated vigorously (26).…”

Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision

“…HCN1 − / − mice cannot follow high-intensity 6 Hz flicker. A different paradigm that provides information about cone activity in the presence of rod system saturation is the 6-Hz scotopic flicker intensity series 17,18 . In this approach, a flicker stimulus of 6 Hz is presented with light intensity increasing in 1/5th logarithmic steps from very dim to very bright.…”