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

Phänomenologie, Erfassung und Bedeutung von Tagesschläfrigkeit als verkehrsrelevanter Faktor bei Risikopopulationen

Seit einigen Jahren steht mit dem pupillographischen Schläfrigkeitstest (PST) ein objektives Messverfahren zur Ermittlung der Tagesschläfrigkeit zur Verfügung, wobei die Zunahme der spontanen Schwankungen des Pupillendurchmessers unter Müdigkeit registriert wird. Es wurde eingesetzt bei verschiedenen Probandengruppen, die einem potenziell erhöhten Risiko von Vigilanzminderungen ausgesetzt sind: chronische Schmerzpatienten (n = 20) beziehungsweise substituierte Heroinabhängige (n = 52) unter Opioiden, ambulante Patienten unter Psychopharmaka (n = 32), Allergiker unter Antihistaminika (n = 40) und medizinisches Nachtdienst-Pflegepersonal (n = 40). Verglichen wurde unter anderem mit zwei Kontrollgruppen (n = 21, n = 10). Bei den Untersuchungen ergaben sich relativ normale Schläfrigkeitswerte bei ambulanten Psychopharmaka-Patienten und Allergikern. Teils exzessiv erhöhte Werte wurden dagegen insbesondere bei substituierten Heroinabhängigen (81 Prozent), opiatversorgten Schmerzpatienten (59 Prozent) und dem Nachtdienstpersonal (70 Prozent) festgestellt

Evaluating a Most Probable Number Method for Assessing the Viability of Great Lakes Protists

To support type approval testing of ballast water management systems we evaluated freshwater viability assessments for protists from the Duluth-Superior harbor of western Lake Superior using the most probable number (MPN) method. Tests were performed using varying temperatures and growth media and were compared to standard microscopic methods for determining live organism densities. Tests were also performed focusing on growth series derived from harbor water, and during an actual land-based test of a treatment system being evaluated for efficacy. We determined that growth of protists during MPN experiments was especially favored under higher temperatures and a growth medium comprising a 50 % solution of Bold Modified Basal Media. This medium also supported the growth of the greatest number of protist taxa. Based on microscopic analysis of live protists use of a treatment system during land-based testing reduced protist densities from 554 – 3000 cells/mL in the untreated water to 12 – 52 cells/mL after treatment. Corresponding assessments using the MPN method estimated respective densities of 1651 – 6060 cells/mL and 0 – 2.8 cells/mL, indicating that MPN likely overestimated viable cells in ambient harbor samples while it underestimated cell densities in treated samples. As asserted in the MPN protocols we confirmed that MPN-estimated protist densities were similar to densities in the protist size class that includes only cells strictly 10 – 50 µm in minimum dimension; protist densities including cells <10 µm were much higher than MPN estimates. However, based on all evaluations of freshly acquired samples containing a wide range of starting densities there was no correlation between MPN- and microscopy-determined densities, regardless of size class. Based on all testing, certain protist taxa were poorly favored during MPN grow-out periods (e.g., the chrysophyte Mallomonas), while others (e.g., free-living centric diatoms) tended to thrive, though there was substantial variability in taxonomic selectivity among tests. These findings contribute important freshwater data to the field of efficacy testing of ballast water treatment systems