A role for talin in presynaptic function

Abstract

Talin, an adaptor between integrin and the actin cytoskeleton at sites of cell adhesion, was recently found to be present at neuronal synapses, where its function remains unknown. Talin interacts with phosphatidylinositol-(4)-phosphate 5-kinase type Iγ, the major phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]–synthesizing enzyme in brain. To gain insight into the synaptic role of talin, we microinjected into the large lamprey axons reagents that compete the talin–PIP kinase interaction and then examined their effects on synaptic structure. A dramatic decrease of synaptic actin and an impairment of clathrin-mediated synaptic vesicle endocytosis were observed. The endocytic defect included an accumulation of clathrin-coated pits with wide necks, as previously observed after perturbing actin at these synapses. Thus, the interaction of PIP kinase with talin in presynaptic compartments provides a mechanism to coordinate PI(4,5)P2 synthesis, actin dynamics, and endocytosis, and further supports a functional link between actin and clathrin-mediated endocytosis.

Dual pools of actin at presynaptic terminals

“…Actin's association with the periphery of presynaptic active sites, its colocalization with endocytic proteins (Bloom et al 2003;Morgan et al 2004), and the disruption of clathrinmediated endocytosis upon disruption of actin polymerization (Bourne et al 2006) have led to an hypothesis that actin is necessary for synaptic vesicle recycling from the endocytic region during stimulation (Brodin and Shupliakov 2006). Stimulation has been shown to alter actin polymerization within synaptosomes (Bernstein and Bamburg 1989) and its distribution in presynaptic terminals of hippocampal neurons in culture (Sankaranarayanan et al 2003) and in lamprey presynaptic terminals (Bloom et al 2003;Shupliakov et al 2002).…”

Integrins as therapeutic targets: lessons and opportunities

“…For the β-integrin CTs, talin is the major interacting cytoplasmic protein 94 . Its binding to the membrane-distal section of the β-tail is a common and necessary event in integrin activation in many cell types and events including T-cell adhesion and migration on ICAM-1 111 , lymphocyte-endothelial cell interactions 112 , macrophage-mediated phagocytosis by α M β 2 integrin 113 , α IIb β 3 -mediated platelet adhesion and spreading 110 and clathrin-mediated endocytosis in the neuronal synapse 114 . Whole-animal disruption of talin expression is lethal in embryonic mice 115 but conditional inhibition of talin expression demonstrates that talin is required specifically for the outside-in activation of integrins in vivo 116 .…”

Talin at a glance

“…Talin (but not vinculin) is also required for both F-actin and integrin accumulation at the immunological synapse (Nolz et al, 2007), and for the chemokine-induced increase in affinity of integrin VLA-4 (α4β1) for VCAM1, which is important in lymphocyte-endothelial cell adhesion (Manevich et al, 2007). In macrophages, talin 1 is required for phagocytosis that is mediated by αMβ2 integrin (complement receptor 3) (Lim et al, 2007), whereas a talin-PIPK1γ90 complex has been shown to play a novel role in clathrin-mediated endocytosis in the neuronal synapse (Morgan et al, 2004).…”