Abstract
Sortilin, also known as Neurotensin Receptor-3, and the sorting-related receptor with type-A repeats (SorLA) are both members of the Vps10p domain receptor family. Initially identified in CNS cells, they are expressed in various other cell types where they exert multiple functions. Although mostly studied for its involvement in Alzheimer’s disease, SorLA has recently been shown to be implicated in immune response by regulating IL-6-mediated signaling, as well as driving monocyte migration. Sortilin has been shown to act as a receptor, as a co-receptor and as an intra- and extracellular trafficking regulator. In the last two decades, deregulation of sortilin has been demonstrated to be involved in many human pathophysiologies, including neurodegenerative disorders (Alzheimer and Parkinson diseases), type 2 diabetes and obesity, cancer, and cardiovascular pathologies such as atherosclerosis. Several studies highlighted different functions of sortilin in the immune system, notably in microglia, pro-inflammatory cytokine regulation, phagosome fusion and pathogen clearance. In this review, we will analyze the multiple roles of sortilin and SorLA in the human immune system and how their deregulation may be involved in disease development.
Highlights
The vacuolar protein sorting 10 protein (Vps10p) domain receptors family is composed of five members: sortilin, sorting-related receptor with type-A repeats (SorLA), sorCS1, sorCS2, and sorCS3
CLF-1 can interact with p28, a subunit of IL-27, to form a cytokine complex activating natural killer cells (NK) and T cells in the presence of IL-6Rα (Crabé et al, 2009) and a potential involvement of sortilin or SorLA in this pathway should be investigated given their role in CLF-1 signaling (Larsen et al, 2010, 2016)
Sortilin and SorLA play incredibly versatile functions depending on their “interactome.” Studies to date emphasize their roles in NTS and neurotrophin signaling pathways in cancer progression, and in cardiovascular, metabolic and neurodegenerative disease
Summary
The vacuolar protein sorting 10 protein (Vps10p) domain receptors family is composed of five members: sortilin, SorLA, sorCS1, sorCS2, and sorCS3. Recent studies have highlighted the involvement of sortilin in the regulation of cytokines secretion during different immune functions, related to cell cytotoxicity and inflammation, through the control of IFN-γ and IL-6 exocytosis. These functions were deduced from experimental models of Sort knock-out (sort1−/−) C57BL/6 mice. CLF-1 can interact with p28, a subunit of IL-27, to form a cytokine complex activating NK and T cells in the presence of IL-6Rα (Crabé et al, 2009) and a potential involvement of sortilin or SorLA in this pathway should be investigated given their role in CLF-1 signaling (Larsen et al, 2010, 2016)
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