Sorting receptor SORLA: cellular mechanisms and implications for disease

Cell Mol Life Sci. 2017 Apr;74(8):1475-1483. doi: 10.1007/s00018-016-2410-z. Epub 2016 Nov 10.

Abstract

Sorting-related receptor with A-type repeats (SORLA) is an intracellular sorting receptor that directs cargo proteins, such as kinases, phosphatases, and signaling receptors, to their correct location within the cell. The activity of SORLA assures proper function of cells and tissues, and receptor dysfunction is the underlying cause of common human malignancies, including Alzheimer's disease, atherosclerosis, and obesity. Here, we discuss the molecular mechanisms that govern sorting of SORLA and its cargo in multiple cell types, and why genetic defects in this receptor results in devastating diseases.

Keywords: Alzheimer’s disease; GGA; Obesity; Protein sorting; Retromer; VPS10P domain receptors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Animals
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Brain / metabolism
  • Brain / pathology
  • Genetic Predisposition to Disease
  • Humans
  • LDL-Receptor Related Proteins / analysis
  • LDL-Receptor Related Proteins / genetics*
  • LDL-Receptor Related Proteins / metabolism*
  • Membrane Transport Proteins / analysis
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism*
  • Nerve Growth Factors / metabolism
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology
  • Protein Conformation
  • Protein Transport
  • Signal Transduction

Substances

  • LDL-Receptor Related Proteins
  • Membrane Transport Proteins
  • Nerve Growth Factors
  • SORL1 protein, human