title: Grb2-associated binder-1 is required for neuregulin-1-induced peripheral nerve myelination.
abstract: Grb2-associated binders (Gabs) are scaffolding proteins implicated in cell signaling via receptor tyrosine kinases including neuregulin-1(NRG1)-ErbB receptor signaling, which is essential for peripheral nerve myelination. Here, we show that the conditional removal of Gab1 from Schwann cells resulted in hypomyelination and abnormal development of Remak bundles. In contrast, hypomyelination was not observed in conventional Gab2 knock-out mice. Tyrosine phosphorylation of Gab1, but not Gab2, in sciatic nerves was upregulated during the myelination period and was found to be suppressed in NRG1-type III(+/-) mice, which display a hypomyelinated phenotype similar to that observed in Gab1 knock-out mice. Gab1 knock-out and NRG1-type III(+/-) mice both exhibited reduced extracellular signal-regulated kinase activity in myelinating nerves. In addition, Krox20, a transcription factor that is critical for myelination, has been identified as a target of the NRG1-Gab1 pathway during the myelination process. Our findings suggest that Gab1 is an essential component of NRG1-type III signaling during peripheral nerve development.
authors.affiliation: Departments of Physiology and.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Departments of Physiology and.
authors.forename: So Young
authors.initials: SY
authors.lastname: Jang
authors.affiliation: Pharmacology, and.
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Departments of Physiology and.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Park
authors.affiliation: Mitochondria Hub Regulation Center (MHRC), Department of Neurology, College of Medicine, Dong-A University, 602-714 Busan, South Korea, and.
authors.forename: Jong Kuk
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Dongkuk University, 100-715 Seoul, South Korea.
authors.forename: Jong Phil
authors.initials: JP
authors.lastname: Kim
authors.affiliation: Departments of Physiology and.
authors.forename: Duk Joon
authors.initials: DJ
authors.lastname: Suh
authors.affiliation: Pharmacology, and.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Departments of Physiology and phwantae@dau.ac.kr.
authors.forename: Hwan Tae
authors.initials: HT
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D020890:Neuregulin-1 / Q000378:metabolism*; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017207:Rats, Sprague-Dawley
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; D020890:Neuregulin-1
keywords: Grb2-associated binders; Schwann cells; conditional knock-out mice; myelination; neuregulin