The absence of a clathrin adapter confers unique polarity essential to proximal tubule function Academic Article uri icon

Overview

MeSH Major

  • Adaptor Protein Complex beta Subunits
  • Adaptor Proteins, Vesicular Transport
  • Cell Polarity
  • Kidney Tubules, Proximal

abstract

  • It is well established that many cognate basolateral plasma membrane proteins are expressed apically in proximal tubule cells thus optimizing the reabsorption capacity of the kidney. The protein clathrin and its adapter proteins normally regulate basolateral polarity. Here we tested whether the unique proximal tubule polarity is dependent on an epithelial-specific basolateral clathrin adapter, AP1B, present in most other epithelia. Quantitative PCR of isolated mouse renal tubules showed that AP1B was absent in proximal tubules but present in medullary and cortical thick ascending limbs of Henle, and cortical collecting ducts. Western blot confirmed the absence of AP1B in three established proximal tubule cell lines. Knockdown of AP1B by shRNA in prototypical distal tubule MDCK cells resulted in redistribution of the basolateral parathyroid hormone receptor, the insulin-like growth factor II receptor/calcium-independent mannose-6-phosphate receptor, and the junctional adhesion molecule, JAM-C, to a proximal tubule-like nonpolar localization. Yeast two-hybrid assays detected direct interactions between the cytoplasmic tails of these plasma membrane proteins and the cargo-binding region of the AP1B complex. Hence, our results show that differential expression of AP1B contributes to normal kidney function and illustrates possible roles of this adapter protein in kidney development, physiology, and pathology.

publication date

  • August 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3684398

Digital Object Identifier (DOI)

  • 10.1038/ki.2010.166

PubMed ID

  • 20531453

Additional Document Info

start page

  • 382

end page

  • 8

volume

  • 78

number

  • 4