Prominin-1 Is a Novel Regulator of Autophagy in the Human Retinal Pigment Epithelium

Bhattacharya, Sujoy; Yin, Jun-Feng; Winborn, Christina S.; Zhang, Qiuhua; Yue, Junming; Chaum, Edward

doi:10.1167/iovs.16-21162

Cited by 58 publications

(80 citation statements)

References 76 publications

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“…It was first identified as a human stem cell-specific marker, but over the last decade its crucial role during the formation and organization of disks within the outer segment of photoreceptors has been recognized [2]. Recently, a new cytoplasmic role of PROM1 in retinal pigment epithelium (RPE) function has also been described -in regulating autophagosome maturation and trafficking [3].…”

Section: Introductionmentioning

confidence: 99%

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1)

et al. 2018

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Background/Aims: To describe the design and baseline characteristics of patients enrolled in the multicenter, prospective natural history study of Stargardt disease type 4. Methods: Fifteen eligible patients aged 6 years and older at baseline, harboring disease-causing variants in the PROM1 gene, and with specified ocular lesions were enrolled. They were examined at baseline using a standard protocol, with 6 monthly follow-up visits for a 2-year period including best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography, fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and quantified on FAF images. Results: Amongst the 15 patients (29 eyes) that were enrolled at 5 centers in the USA and Europe, 10 eyes (34.5%) had areas of DDAF with an average lesion area of 3.2 ± 3.5 mm² (range 0.36–10.39 mm²) at baseline. The mean retinal sensitivity of the posterior pole derived from mesopic MP was 8.8 ± 5.8 dB. Conclusions: Data on disease progression in PROM1-related retinopathy from this study will contribute to the characterization of the natural history of disease and the exploration of the utility of several modalities to track progression and therefore to potentially be used in future interventional clinical trials.

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Section: Introductionmentioning

confidence: 99%

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1)

et al. 2018

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“…Interestingly, prom1 also plays a role in autophagy where a phosphorylationdependent interaction with g-aminobutyric acid receptor-associated protein (GABARAP), an initiator of autophagy, leads to the suppression of GABARAP-mediated ULK1 kinase activation and the subsequent initiation of autophagy (82,83). The prom1 phosphorylation could link ciliogenesis and autophagy (84,85), which in turn may regulate the cell proliferation versus differentiation (86).…”

Section: Discussionmentioning

confidence: 99%

Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3

Jászai

Thamm

Karbanová

et al. 2020

Journal of Biological Chemistry

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Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin–Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of WT PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor–like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights into ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.

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“…e Prominin-1 (Prom1) gene can regulate autophagy by inhibiting mTOR in RPE. Induction of Prom1-dependent autophagy during aging may be an intrinsic defense mechanism, which enables the RPE cells to cope with increased oxidative burden [101].…”

Section: Corneal Dystrophymentioning

confidence: 99%

Autophagy and Age-Related Eye Diseases

Yang

Pan

Zhao

et al. 2019

BioMed Research International

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Background. Autophagy is a catabolic process that depends on the lysosome. It is usually used to maintain cellular homeostasis, survival and development by degrading abnormal substances and dysfunctional organelles, especially when the cell is exposed to starvation or other stresses. Increasing studies have reported that autophagy is associated with various eye diseases, of which aging is one of the important factors. Objective. To summarize the functional and regulatory role of autophagy in ocular diseases with aging, and discuss the possibility of autophagy-targeted therapy in age-related diseases. Methods. PubMed searches were performed to identify relevant articles published mostly in the last 5 years. The key words were used to retrieve including “autophagy”, “aging”, “oxidative stress AND autophagy”, “dry eye AND autophagy”, “corneal disease AND autophagy”, “glaucoma AND autophagy”, “cataract AND autophagy”, “AMD AND autophagy”, “cardiovascular diseases AND autophagy”, “diabetes AND autophagy”. After being classified and assessed, the most relevant full texts in English were chosen. Results. Apart from review articles, more than two research articles for each age-related eye diseases related to autophagy were retrieved. We only included the most relevant and recent studies for summary and discussion. Conclusion. Autophagy has both protective and detrimental effects on the progress of age-related eye diseases. Different types of studies based on certain situations in vitro showed distinct results, which do not necessarily coincide with the actual situation in human bodies completely. It means the exact role and regulatory function of autophagy in ocular diseases remains largely unknown. Although autophagy as a potential therapeutic target has been proposed, many problems still need to be solved before it applies to clinical practice.

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Prominin-1 Is a Novel Regulator of Autophagy in the Human Retinal Pigment Epithelium

Cited by 58 publications

References 76 publications

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1)

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1)

Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3

Autophagy and Age-Related Eye Diseases

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