Редактирование: SLC36A4 (раздел)

==Publications==

{{medline-entry
|title=The amino acid transporter [[SLC36A4]] regulates the amino acid pool in retinal pigmented epithelial cells and mediates the mechanistic target of rapamycin, complex 1 signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28083894
|abstract=The dry (nonneovascular) form of age-related macular degeneration (AMD), a leading cause of blindness in the elderly, has few, if any, treatment options at present. It is characterized by early accumulation of cellular waste products in the retinal pigmented epithelium ([[RPE]]); rejuvenating impaired lysosome function in [[RPE]] is a well-justified target for treatment. It is now clear that amino acids and vacuolar-type H  -ATPase (V-ATPase) regulate the mechanistic target of rapamycin, complex 1 (mTORC1) signaling in lysosomes. Here, we provide evidence for the first time that the amino acid transporter [[SLC36A4]]/proton-dependent amino acid transporter (PAT4) regulates the amino acid pool in the lysosomes of [[RPE]]. In Cryba1 (gene encoding βA3/A1-crystallin) KO (knockout) mice, where PAT4 and amino acid levels are increased in the [[RPE]], the transcription factors EB (TFEB) and E3 (TFE3) are retained in the cytoplasm, even after 24 h of fasting. Consequently, genes in the coordinated lysosomal expression and regulation (CLEAR) network are not activated, and lysosomal function remains low. As these mice age, expression of [[[[RPE]]65]] and lecithin retinol acyltransferase (LRAT), two vital visual cycle proteins, decreases in the [[RPE]]. A defective visual cycle would possibly slow down the regeneration of new photoreceptor outer segments (POS). Further, photoreceptor degeneration also becomes obvious during aging, reminiscent of human dry AMD disease. Electron microscopy shows basal laminar deposits in Bruch's membrane, a hallmark of development of AMD. For dry AMD patients, targeting PAT4/V-ATPase in the lysosomes of [[RPE]] cells may be an effective means of preventing or delaying disease progression.
|mesh-terms=* Aging
* Amino Acid Transport Systems
* Amino Acids
* Animals
* Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
* Crystallins
* Cytosol
* Epithelial Cells
* Gene Regulatory Networks
* Lysosomes
* Mechanistic Target of Rapamycin Complex 1
* Mice, Knockout
* Multiprotein Complexes
* Phosphorylation
* Protein Binding
* Retinal Photoreceptor Cell Outer Segment
* Retinal Pigment Epithelium
* Signal Transduction
* TOR Serine-Threonine Kinases
* Visual Pathways
* beta-Crystallin A Chain
|keywords=* age-related macular degeneration
* amino acid transporter (PAT4/SLC36A4)
* complex 1 (mTORC1)
* coordinated lysosomal expression and regulation (CLEAR) network
* lysosomes; mechanistic target of rapamycin
* mouse model
* photoreceptor degeneration
* retinal pigmented epithelium (RPE)
* signal transduction
* transcription factors EB (TFEB) and E3 (TFE3)
* visual cycle proteins
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334531
}}