Profilins are small proteins that form complexes with G‐actin and phosphoinositides and are therefore considered to link the microfilament system to signal transduction pathways. In addition, they bind to poly‐L‐proline, but the biological significance of this interaction is not yet known. The recent molecular cloning of the vasodilator‐stimulated phosphoprotein (VASP), an established in vivo substrate of cAMP‐ and cGMP‐dependent protein kinases, revealed the presence of a proline‐rich domain which prompted us to investigate a possible interaction with profilins. VASP is a microfilament and focal adhesion associated protein which is also concentrated in highly dynamic regions of the cell cortex. Here, we demonstrate that VASP is a natural proline‐rich profilin ligand. Human platelet VASP bound directly to purified profilins from human platelets, calf thymus and birch pollen. Moreover, VASP and a novel protein were specifically extracted from total cell lysates by profilin affinity chromatography and subsequently eluted either with poly‐L‐proline or a peptide corresponding to a proline‐rich VASP motif. Finally, the subcellular distributions of VASP and profilin suggest that both proteins also interact within living cells. Our data support the hypothesis that profilin and VASP act in concert to convey signal transduction to actin filament formation.

Vertebrate synapsins are abundant synaptic vesicle phosphoproteins that have been proposed to fine-regulate neurotransmitter release by phosphorylation-dependent control of synaptic vesicle motility. However, the consequences of a total lack of all synapsin isoforms due to a knock-out of all three mouse synapsin genes have not yet been investigated. In Drosophila a single synapsin gene encodes several isoforms and is expressed in most synaptic terminals. Thus the targeted deletion of the synapsin gene of Drosophila eliminates the possibility of functional knock-out complementation by other isoforms. Unexpectedly, synapsin null mutant flies show no obvious defects in brain morphology, and no striking qualitative changes in behaviour are observed. Ultrastructural analysis of an identified 'model' synapse of the larval nerve muscle preparation revealed no difference between wild-type and mutant, and spontaneous or evoked excitatory junction potentials at this synapse were normal up to a stimulus frequency of 5 Hz. However, when several behavioural responses were analysed quantitatively, specific differences between mutant and wild-type flies are noted. Adult locomotor activity, optomotor responses at high pattern velocities, wing beat frequency, and visual pattern preference are modified. Synapsin mutant flies show faster habituation of an olfactory jump response, enhanced ethanol tolerance, and significant defects in learning and memory as measured using three different paradigms. Larval behavioural defects are described in a separate paper. We conclude that Drosophila synapsins play a significant role in nervous system function, which is subtle at the cellular level but manifests itself in complex behaviour.

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The present investigation strongly supports the hypothesis that PDGF-isoforms are major stimulators of proliferation of Tenon's capsule fibroblasts after glaucoma filtering surgery while TGF-beta-isoforms are essential for the transformation of Tenon's capsule fibroblasts into myofibroblasts.

Confluent AKR-2B fibroblasts rapidly desintegrate upon removal of serum until a final density of approximately 50% of the initial value was reached after 12 h. This density remained unchanged for at least 48 h. Platelet-derived growth factor (PDGF)-BB stimulated more than 95% of these cells to divide. PDGF-AB or -BB added immediately after serum removal caused complete survival of the cells, but did not stimulate cell division as demonstrated by two-dimensional DNA flow cytometry. PDGF-AA was less effective leading to approximately 75% of the initial cell density. This effect could be augmented by the addition of ocadaic acid, a potent phosphatase inhibitor, suggesting that protein phosphorylation plays a role in this process. By using tyrphostin AG807 it was demonstrated that the signaling mechanism for survival requires receptor tyrosine autophosphorylation.