Figure 1
CR3 both activates and downregulates myelin phagocytosis – a schematic representation of the working hypothesis and experimental design. Binding of myelin to CR3 initiates structural changes characteristic of phagocytosis (marked by ellipses). Filopodia-like membrane protrusions engulf myelin as they extend and then pull myelin in as they retract. Production of filopodia depends on F-actin remodeling, which active unphosphorylated cofilin advances (↓) and inactive p-cofilin impedes (⟂) [26–28]. Therefore, phagocytosis is expected to be reduced when cofilin is inactivated by shifting the balance from cofilin to p-cofilin through activation of LIMK and/or TESK, for example, by RhoA and ROCK, and/or downregulation of phosphatases SSH and CIN. CR3 downregulates phagocytosis by activating Syk, which in turn advances the inactive phosphorylated state of cofilin. How Syk promotes cofilin inactivation is yet to be determined. CR3 activates myelin phagocytosis by activating K-Ras and its downstream effectors in a galectin-3-dependent manner [30–33]. Subsequently, retraction of filopodia is aided by contraction that Ca+2-calmodulin-dependent MLCK (myosin light chain kinase) activates and F-actin and non-muscle myosin carry out [34]. Not all possible interactions are shown.