Abstract
Epidermal growth factor receptor (EGFR) is the first discovered member of the receptor tyrosine kinase superfamily and plays a fundamental role during embryogenesis and in adult tissues, being involved in growth, differentiation, maintenance and repair of various tissues and organs. The role of EGFR in the regulation of tissue development and homeostasis has been thoroughly investigated and it has also been demonstrated that EGFR is a driver of tumorigenesis. In the nervous system, other growth factors, and thus other receptors, are important for growth, differentiation and repair of the tissue, namely neurotrophins and neurotrophins receptors. For this reason, for a long time, the role of EGFR in the nervous system has been underestimated and poorly investigated. However, EGFR is expressed both in the central and peripheral nervous systems and it has been demonstrated to have specific important neurotrophic functions, in particular in the central nervous system. This review discusses the role of EGFR in regulating differentiation and functions of neurons and neuroglia. Furthermore, its involvement in regeneration after injury and in the onset of neurodegenerative diseases is examined.
Highlights
The epidermal growth factor receptor (EGFR, known as ErbB1 or HER-1) belongs to the receptor tyrosine kinase (RTK) superfamily, which consists of other three members, ErbB2/Neu/HER-2, ErbB3/HER-3 and ErbB4/HER-4 [1,2]
These results demonstrate the importance of Epidermal growth factor receptor (EGFR) in neural stem cells (NSCs) selfrenewal and that loss of EGFR signaling in cells derived from subventricular zone (SVZ) leads them to differentiate preferentially into glia [55]
EGFR seems to be downregulated in oligodendrocyte lineage in the adult but, after a demyelinating damage, factors produced in the SVZ by microglia stimulate NSCs to differentiate into oligodendrocyte precursor cells (OPCs) and EGFR expression and activation in oligodendrocyte lineage stimulates oligodendrogenesis to repair the damage, recapitulating what happens during development
Summary
The epidermal growth factor receptor (EGFR, known as ErbB1 or HER-1) belongs to the receptor tyrosine kinase (RTK) superfamily, which consists of other three members, ErbB2/Neu/HER-2, ErbB3/HER-3 and ErbB4/HER-4 [1,2]. RAB7-positive endosomes and lysosomes in the perinuclear region where are its internalized endocytosis and of theyEGFR are recycled back to by plasma membrane degradation through occurs clathrin-mediate [15] (Figure 2B). EGFR membrane is not marked for degradation [16].[14] This process regulated by EGF ubiquitinates which is recognized by the ubiquitin-dependent adaptors of the endosomal sorting concentration.EGFR, when. Fact, inwith the could be recycled, through exosomes degraded following fusion ofInMVBs case of the WNT binds to both low-density lipoprotein receptor-related and lysosomes [20]. EGFR deletion is detrimental for progenitors, cells; PNS: peripheral nervous system; CNS: central system; GFAP: fibrillary acid protein; astrocytes, oligodendrocytes and neurons. Functions in regeneration after injury and its involvement in the onset and progression of nervous system diseases
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