title: Expression of the transmembrane lysosomal protein SCARB2/Limp-2 in renin secretory granules controls renin release.
abstract: OBJECTIVE
  Renin processing and storage is believed to occur in lysosome-like structures in the afferent arteriole. SCARB2/Limp-2 is a transmembrane lysosomal protein responsible for the intracellular trafficking of β-glucocerebrosidase. This study aimed to confirm the expression of SCARB2/Limp-2 in renin secretory granules, and explore its role in renin processing and secretion.
  
  
  METHODS
  Co-localisation studies of (pro)renin with lysosomal membrane proteins, SCARB2/Limp-2, LAMP-1 and LAMP-2, were performed in mouse and human kidney sections. Intrarenal expression and secretion of (pro)renin in wild-type (WT) and Limp-2(-/-) mice were compared with and without stimulation.
  
  
  RESULTS
  SCARB2/Limp-2, LAMP-1 and LAMP-2 co-localised with (pro)- renin in mouse and human kidney. Plasma renin concentration was increased in Limp-2(-/-) mice when compared to WT littermates. No change in (pro)renin expression, however, was observed in Limp-2(-/-) mouse kidney cortex by immunofluorescence microscopy, Western blotting, quantitative RT-PCR or the ultrastructural appearance of renin secretory granules. Acute stimulation of renin release by isoprenaline or hydralazine was similar in WT and Limp-2(-/-) mice. Following chronic salt restriction, however, immunofluorescence microscopy showed less (pro)renin expressed in Limp-2(-/-) compared with WT mouse kidneys, and there was significantly less prorenin but not renin by Western blotting in Limp-2(-/-) mouse kidney cortex, despite no difference in circulating renin levels.
  
  
  CONCLUSIONS
  Renin secretory granules possess integral lysosomal proteins, confirming that they are indeed modified lysosomes. Limp-2 deficiency leads to a minor increase in circulating renin. Limp-2, however, is not required for acute or chronic stimulation of renin release.
authors: Department of Nephrology, Austin Health, Melbourne, Vic., Australia.
authors: D
authors: D
authors: Lee
authors: M J
authors: MJ
authors: Desmond
authors: S A
authors: SA
authors: Fraser
authors: M
authors: M
authors: Katerelos
authors: K
authors: K
authors: Gleich
authors: S F
authors: SF
authors: Berkovic
authors: D A
authors: DA
authors: Power
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism*; D018955:CD36 Antigens / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007668:Kidney / Q000098:blood supply; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000096:biosynthesis*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D051116:Receptors, Scavenger / Q000096:biosynthesis*; D012083:Renin / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D018955:CD36 Antigens; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; D012083:Renin; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C497811:LAMP2 protein, human; C074299:SCARB2 protein, human; C489452:Scarb2 protein, mouse