Journal article

Tubular proteinuria in mice and humans lacking the intrinsic lysosomal protein SCARB2/Limp-2

MJ Desmond, D Lee, SA Fraser, M Katerelos, K Gleich, P Martinello, YQ Li, MC Thomas, R Michelucci, AJ Cole, P Saftig, M Schwake, D Stapleton, SF Berkovic, DA Power

American Journal of Physiology: Renal Physiology | AMER PHYSIOLOGICAL SOC | Published : 2011


Deficiency of the intrinsic lysosomal protein human scavenger receptor class B, member 2 (SCARB2; Limp-2 in mice) causes collapsing focal and segmental glomerular sclerosis (FSGS) and myoclonic epilepsy in humans, but patients with no apparent kidney damage have recently been described. We now demonstrate that these patients can develop tubular proteinuria. To determine the mechanism, mice deficient in Limp-2, the murine homolog of SCARB2, were studied. Most low-molecular-weight proteins filtered by the glomerulus are removed in the proximal convoluted tubule (PCT) by megalin/cubilin-dependent receptor-mediated endocytosis. Expression of megalin and cubilin was unchanged in Limp-2(-/-) mice,..

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Funding Acknowledgements

M. J. Desmond and D. Lee were supported by Postgraduate Scholarships from the National Health and Medical Research Council, Australia. D. Lee has also been supported by the Jacquot Bequest, Royal Australasian College of Physicians. This work was supported by a National Health and Medical Research Council Project Grant to D. A. Power and a Program Grant to S. F. Berkovic.