Fig. 1.

Initiation of Cytoneme Formation. A Morphogen initiation of cytoneme budding. Following maturation and secretory transport, morphogens engage cognate deployment proteins and co-receptors at the cell surface to initiate intracellular signaling through effector kinases and GTPases. Kinases activate substrates including Actin-Binding Proteins (ABPs) and Guanine nucleotide Exchange Factors (GEFs), which in turn promote GTP binding to small GTPases. GTPase effectors polymerize actin at these sites. For WNT signaling, Planar Cell Polarity (PCP) proteins contribute to deployment. Flotillin is frequently detected at sites of morphogen clustering, suggesting that it may contribute to aggregation of transmembrane and lipid-modified molecules involved in this process. B Cytoneme extension. Following activation of actin-polymerization machinery, actin is assembled into linear bundles that expand the cell surface to form a cytoneme bud. BAR domain-containing proteins are activated by Cdc42 to induce membrane curvature and concentrate actin machinery at these sites. In these cases, BAR–domain protein interactor Wiskott-Aldrich Syndrome Protein (N-WASP) promotes branched actin assembly to provide a scaffold for linear actin filament assembly. The unbranched actin polymerization, accomplished by Ena/VASP family members and/or formin proteins, then acts to extend the nascent cytoneme. Linear actin filaments are cross-linked upon binding by Fascin