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Cover  Dynamin at Novel Plasma Membrane-Cytoskeletal Structures in Migrating Cells. The dynamins are an expanding family of large GTPase with mechanochemical properties that have traditionally been implicated in the early stages of vesicle formation during endocytosis. Recent studies have demonstrated a role for conventional dynamins in a variety of novel diverse locations such as endosomes, the trans-Golgi network, and the midbody of dividing cells. Recent studies by several groups have shown that one form of dynamin (Dyn2) appears to mediate the formation of several related, but distinct, dynamic plasma membrane structures that support tumor cell migration and invasion. Left, a human melanoma cell stained in green for dynamin-2 (Dyn2) reveals numerous circular "invadopodia" structures along the ventral surface.

Invadopodia are specialized membrane protrusions and active sites of protease release utilized by tumor cells to degrade the extracellular matrix and facilitate cell invasion and metastasis. Large areas of degraded matrix are depicted in red. As shown by Buccione and colleagues, in this issue, Dyn2 is localized to invadopodia and is required for their establishment and function. Right, Dyn2 function is required for the formation of large transient, dorsal plasma membrane structues, or "waves" in growth factor-stimulated cells. A mouse 3T3 cell fixed 5 min after stimulation with platelet-derived growth factor (PDGF) and stained for Dyn2 (green) and actin (red). Large punctate wave structures, enriched in Dyn2, have formed along the dorsal leading edge of the cell and coincide with the regulated disassembly of actin stress fibers. As reported by McNiven and coworkers in this issue, these structures appear to mediate reorganization of the actin cytoskeleton to promote lamellipodial extension prior to cell motility.Roberto Buccione and Mark McNiven