Receptor-Mediated Endocytosis in the Proximal Tubule

Annu Rev Physiol. 2017 Feb 10;79:425-448. doi: 10.1146/annurev-physiol-022516-034234. Epub 2016 Oct 28.


Cells lining the proximal tubule (PT) of the kidney are highly specialized for apical endocytosis of filtered proteins and small bioactive molecules from the glomerular ultrafiltrate to maintain essentially protein-free urine. Compromise of this pathway results in low molecular weight (LMW) proteinuria that can progress to end-stage kidney disease. This review describes our current understanding of the endocytic pathway and the multiligand receptors that mediate LMW protein uptake in PT cells, how these are regulated in response to physiologic cues, and the molecular basis of inherited diseases characterized by LMW proteinuria.

Keywords: Dent disease; Lowe syndrome; albumin; apical; cubilin; cystinosis; kidney; megalin; proteinuria.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Endocytosis / physiology*
  • Humans
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / physiology
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / physiology*
  • Proteinuria / metabolism
  • Proteinuria / physiopathology
  • Receptors, Cell Surface / metabolism*


  • Receptors, Cell Surface