J Mol Med DOI 10.1007/s00109-014-1152-3

MOLECULES IN MEDICINE

Sorting receptor sortilin—a culprit in cardiovascular and neurological diseases Anne-Sophie Carlo & Anders Nykjaer & Thomas E. Willnow

Received: 5 February 2014 / Accepted: 19 February 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract Sortilin is a sorting receptor that directs target proteins, such as growth factors, signaling receptors, and enzymes, to their destined location in secretory or endocytic compartments of cells. The activity of sortilin is essential for proper function of not only neurons but also non-neuronal cell types, and receptor (dys)function emerges as a major cause of malignancies, including hypercholesterolemia, retinal degeneration, neuronal cell loss in stroke and spinal cord injury, or Alzheimer’s disease and other neurodegenerative disorders. In this article, we describe the molecular mechanisms of sortilin action in protein sorting and signaling and how modulation of receptor function may offer novel therapeutic strategies for treatment of common diseases of the cardiovascular and nervous systems.

(e.g., to lysosomes). Trafficking of proteins is controlled by their interaction with sorting receptors and cytosolic adaptors capable of moving between distinct cellular organelles. Recent years witnessed the functional elucidation of major sorting pathways in mammalian cell types. These studies uncovered the molecular mechanisms of protein sorting machineries, characterized their relevance for normal physiology, and identified new targets for treatment of human diseases. This mini review describes sortilin, a multifunctional sorting receptor that directs signaling molecules, cell surface receptors, and metabolites between secretory and endocytic compartments and that emerges as a major disease gene in cardiovascular, neurological, and neurodegenerative disorders.

Keywords Protein sorting . VPS10P domain receptors . Alzheimer disease . Frontotemporal lobar degeneration . Apolipoprotein E

Cell biology of sortilin

Correct sorting of cellular proteins to their destined location in subcellular compartments is essential for proper function of cells and tissues, and defects in protein sorting are the cause of many devastating diseases. Sorting of proteins may involve retention in a specific cell organelle (e.g., in the Golgi), retrieval back to a compartment (e.g., to the endoplasmic reticulum), or forward sorting to a subcellular destination A.

Sorting receptor sortilin-a culprit in cardiovascular and neurological diseases.

Sortilin is a sorting receptor that directs target proteins, such as growth factors, signaling receptors, and enzymes, to their destined location in s...
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