Dynamin as a Mover and Pincher during Cell Migration and Invasion

The large GTPase dynamin, long known for its role in endocytosis, has most recently been implicated as a facilitator of cell migration and invasion. Recent observations link dynamin to the cycle of membrane expansion and retraction essential for cell motility. Its role in actin polymerization, membrane deformation and vesiculation, and focal adhesion dynamics are all important for this process, and the new findings provide exciting directions for studies of this ubiquitous and diverse protein family

A Dynamin-3 Spliced Variant Modulates the Actin/Cortactin-Dependent Morphogenesis of Dendritic Spines

Immature dendrites extend many actin-rich filopodial structures that can be replaced by synapse-containing dendritic spines as the neuron matures. The large GTPase dynamin-3 (Dyn3) is a component of the postsynapse in hippocampal neurons but its function is undefined. Here, we demonstrate that a specific Dyn3 variant (Dyn3baa) promotes the formation of immature dendritic filopodia in cultured neurons. This effect is dependent upon Dyn3 GTPase activity and a direct interaction with the F-actin-binding protein cortactin. Consistent with these findings, Dyn3baa binds to cortactin with a 200% higher affinity than Dyn3aaa, a near identical isoform that does not induce dendritic filopodia when expressed in cultured neurons. Finally, levels of Dyn3baa-encoding mRNA are tightly regulated during neuronal maturation and are markedly upregulated during synaptogenesis. Together, these findings provide the first evidence that an enhanced interaction between a specific Dyn3 splice variant and cortactin modulate actin-membrane dynamics in developing neurons to regulate the morphogenesis of dendritic spines. Supplementary material available online at http://jcs.biologists.org/cgi/content/full/118/6/1279/DC

Receptor Biology

This book is geared to every student in biology, pharmacy and medicine who needs to become familiar with receptor mediated signaling. The text starts with explaining some basics in membrane biochemistry, hormone biology and the concept of receptor based signaling as the main form of communication between cells and of cells with the environment. It goes on covering each receptor superfamily in detail including their structure and evolutionary context. The last part focuses exclusively on examples where thorough knowledge of receptors is critical: pharmaceutical research, developmental biology, neurobiology and evolutionary biology. Richly illustrated, the book is perfectly suited for all courses covering receptor based signaling, regardless whether they are part of the biology, medicine or pharmacology program.https://digitalcommons.linfield.edu/linfauth/1068/thumbnail.jp

Distinct phospho-forms of cortactin differentially regulate actin polymerization and focal adhesions

Cortactin is an actin-binding protein that is overexpressed in many cancers and is a substrate for both tyrosine and serine/threonine kinases. Tyrosine phosphorylation of cortactin has been observed to increase cell motility and invasion in vivo, although it has been reported to have both positive and negative effects on actin polymerization in vitro. In contrast, serine phosphorylation of cortactin has been shown to stimulate actin assembly in vitro. Currently, the effects of cortactin serine phosphorylation on cell migration are unclear, and furthermore, how the distinct phospho-forms of cortactin may differentially contribute to cell migration has not been directly compared. Therefore, we tested the effects of different tyrosine and serine phospho-mutants of cortactin on lamellipodial protrusion, actin assembly within cells, and focal adhesion dynamics. Interestingly, while expression of either tyrosine or serine phospho-mimetic cortactin mutants resulted in increased lamellipodial protrusion and cell migration, these effects appeared to be via distinct processes. Cortactin mutants mimicking serine phosphorylation appeared to predominantly affect actin polymerization, whereas mutation of cortactin tyrosine residues resulted in alterations in focal adhesion turnover. Thus these findings provide novel insights into how distinct phospho-forms of cortactin may differentially contribute to actin and focal adhesion dynamics to control cell migration

Caveolin-1 Induces Formation of Membrane Tubules That Sense Actomyosin Tension and Are Inhibited by Polymerase I and Transcript Release Factor/Cavin-1

We found that PTRF/cavin-1 is lost coordinately with caveolin-1 in some cancer cells. When reexpressed in these cells, caveolin-1 formed membrane tubules that were under actomyosin-induced tension and recruited Rab8 and EHD proteins. PTRF/cavin-1 inhibited tubule formation by caveolin-1, showing a new function for the protein