MYRF Is a Membrane-Associated Transcription Factor That Autoproteolytically Cleaves to Directly Activate Myelin Genes

Abstract

Oligodendrocyte development and myelination rely on an unusual membrane-associated transcription factor that shares functional domains with bacteriophage proteins.

Integrin-Linked Kinase (ILK) Deletion Disrupts Oligodendrocyte Development by Altering Cell Cycle

“…Of particular importance are the proteins that regulate the cytoskeleton organization by linking F-actin to the integrin cytoplasmic tail (Wu and Dedhar, 2001). In addition, integrin signals can be mediated through ILK, which functions as a molecular scaffold at cell-extracellular matrix adhesion sites and participates in signal transduction pathways that control cell survival, differentiation, morphology, proliferation, and gene expression in mammalian cells (Chun et al, 2003). Within focal adhesion (FA) complexes, ILK interacts with other FA proteins such as paxillin, affixin, and parvin (Tu et al, 2001).…”

“…Axonal ensheathment by Schwann cells in the PNS and oligodendrocytes in the CNS is crucial for rapid action potential conduction. Numerous molecules and growth factors have been described that influence myelination and remyelination positively or negatively (Emery, 2010;Nave, 2010;Franklin et al, 2012;Zuchero and Barres, 2013;McKenzie et al, 2014;Fields, 2015;Tsai et al, 2016) and act through a number of known transcription factors (Emery et al, 2009;Zhu et al, 2012;Bujalka et al, 2013;Hornig et al, 2013;Yu et al, 2013;Silbereis et al, 2014). The pathways connecting these extracellular signals with the transcriptional changes in oligodendrocytes are still being investigated (Colognato and Tzvetanova, 2011;Ahrendsen and Macklin, 2013;Wood et al, 2013;Bercury and Macklin, 2015;Gaesser and Fyffe-Maricich, 2016).…”

“…The pathways connecting these extracellular signals with the transcriptional changes in oligodendrocytes are still being investigated (Colognato and Tzvetanova, 2011;Ahrendsen and Macklin, 2013;Wood et al, 2013;Bercury and Macklin, 2015;Gaesser and Fyffe-Maricich, 2016). Integrin-linked kinase (ILK) is a multifunctional intracellular effector of cell-matrix interactions that regulates many cellular processes (Hannigan et al, 1996;Persad et al, 2000;Koul et al, 2005;Chiswell et al, 2008;McDonald et al, 2008a;Dagnino, 2011;Widmaier et al, 2012). However, its role in oligodendrocyte precursor cells (OPCs) is less clear.…”

“…ILK is essential during PNS development (Pereira et al, 2009), but its role in CNS myelination is less clear. Oligodendrocyte process extension and differentiation in vitro requires ILK (Chun et al, 2003), which acts via Rho-GTPase to regulate the actin cytoskeleton and oligodendrocyte growth cones (O'Meara et al, 2013;Michalski et al, 2016). In other cells, in addition to its cytoskeletal role, ILK is involved in cell replication and oncogenesis (McDonald et al, 2008a;McDonald et al, 2008b;Fielding et al, 2011).…”

Integrin-Linked Kinase (ILK) Deletion Disrupts Oligodendrocyte Development by Altering Cell Cycle

“…However, its role in oligodendrocyte precursor cells (OPCs) is less clear. ILK was originally defined as a binding partner of integrin ␤1 and is well known for its dual actions, both as a scaffolding molecule (Chiswell et al, 2008;Dagnino, 2011) and as a serine/threonine protein kinase (Berken et al, 2003;Troussard et al, 2003;Okamura et al, 2007;Watzka et al, 2011). It modulates many downstream activators, in part by phosphorylating Akt, glycogen synthase kinase (GSK) 3␤, and myosin light chain (Novak and Dedhar, 1999;Persad et al, 2000;Grashoff et al, 2003).…”