Charming neighborhoods on the cell surface: Plasma membrane microdomains regulate receptor tyrosine kinase signaling

Receptor tyrosine kinases (RTK) are an important family of growth factor and hormone receptors that regulate many aspects of cellular physiology. Ligand binding by RTKs at the plasma membrane elicits activation of many signaling intermediates. The spatial and temporal regulation of RTK signaling within cells is an important determinant of receptor signaling outcome. In particular, the compartmentalization of the plasma membrane into a number of microdomains allows context-specific control of RTK signaling. Indeed various RTKs are recruited to and enriched within specific plasma membrane microdomains under various conditions, including lipid-ordered domains such as caveolae and lipid rafts, clathrin-coated structures, tetraspanin-enriched microdomains, and actin-dependent protrusive membrane microdomains such as dorsal ruffles and invadosomes. We examine the evidence for control of RTK signaling by each of these plasma membrane microdomains, as well as molecular mechanisms for how this spatial organization controls receptor signaling. •Receptor tyrosine kinases (RTKs) control many aspects of cellular and systemic physiology.•RTK function is controlled by spatial organization of signaling intermediates at many levels within cells.•The plasma membrane is comprised of numerous microdomains, each enriched in specific lipid and protein signals.•RTKs are each selectively recruited to various specific plasma membrane microdomains under various contexts.•Many of these defined plasma membrane microdomains regulate RTK signaling and function.