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Loss of melanoregulin (MREG) enhances cathepsin-D secretion by the retinal pigment epithelium.


ABSTRACT: Cathepsin-D (Cat-D) is a major proteolytic enzyme in phagocytic cells. In the retinal pigment epithelium (RPE), it is responsible for the daily degradation of photoreceptor outer segments (POSs) to maintain retinal homeostasis. Melanoregulin (MREG)-mediated loss of phagocytic capacity has been linked to diminished intracellular Cat-D activity. Here, we demonstrate that loss of MREG enhances the secretion of intermediate Cat-D (48 kDa), resulting in a net enhancement of extracellular Cat-D activity. These results suggest that MREG is required to maintain Cat-D homeostasis in the RPE and likely plays a protective role in retinal health. In this regard, in the Mreg dsu/dsu mouse, we observe increased basal laminin. Loss of the Mreg dsu allele is not lethal and therefore leads to slow age-dependent changes in the RPE. Thus, we propose that this model will allow us to study potential dysregulatory functions of Cat-D in retinal disease.

SUBMITTER: Frost LS 

PROVIDER: S-EPMC3912860 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Loss of melanoregulin (MREG) enhances cathepsin-D secretion by the retinal pigment epithelium.

Frost Laura S LS   Lopes Vanda S VS   Stefano Frank P FP   Bragin Alvina A   Williams David S DS   Mitchell Claire H CH   Boesze-Battaglia Kathleen K  

Visual neuroscience 20130423 3


Cathepsin-D (Cat-D) is a major proteolytic enzyme in phagocytic cells. In the retinal pigment epithelium (RPE), it is responsible for the daily degradation of photoreceptor outer segments (POSs) to maintain retinal homeostasis. Melanoregulin (MREG)-mediated loss of phagocytic capacity has been linked to diminished intracellular Cat-D activity. Here, we demonstrate that loss of MREG enhances the secretion of intermediate Cat-D (48 kDa), resulting in a net enhancement of extracellular Cat-D activi  ...[more]

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