The Synaptic Vesicle Protein SV2 Is Complexed with an α5-Containing Laminin on the Nerve Terminal Surface

Abstract

Interactions between growing axons and synaptic basal lamina components direct the formation of neuromuscular junctions during nerve regeneration. Isoforms of laminin containing ␣5 or ␤2 chains are potential basal lamina ligands for these interactions. The nerve terminal receptors are unknown. Here we show that SV2, a synaptic vesicle transmembrane proteoglycan, is complexed with a 900-kDa laminin on synaptosomes from the electric organ synapse that is similar to the neuromuscular junctions. Although two laminins are present on synaptosomes, only the 900-kDa laminin is associated with SV2. Other nerve terminal components are absent from this complex. The 900-kDa laminin contains an ␣5, a ␤1, and a novel ␥ chain. To test whether SV2 directly binds the 900-kDa laminin, we looked for interaction between purified SV2 and laminin-1, a laminin isoform with a similar structure. We find SV2 binds with high affinity to purified laminin-1. Our results suggest that a synaptic vesicle component may act as a laminin receptor on the presynaptic plasma membrane; they also suggest a mechanism for activity-dependent adhesion at the synapse.

Synaptic Vesicle Protein 2 Enhances Release Probability at Quiescent Synapses

“…The observation that SV2 binds the extracellular matrix protein laminin suggested that SV2 could play a role in synapse formation (Carlson, 1996;Son et al, 2000). To determine whether reduced EPSC amplitude was attributable to reduced synapse formation, we compared synapse number in wild-type and SV2 knock-out neurons.…”

The Basement Membrane/Basal Lamina of Skeletal Muscle

“…Receptors presumably include integrins, which bind laminins generally; indeed, integrin ␣ 3 is concentrated at active zones (27). In addition, laminins-9 and -11 co-purify with distinct presynaptic membrane components, the calcium channels that trigger transmitter release and the vesicle-associated protein, SV2, respectively (58,59). These associations raise the possibility that laminins could organize presynaptic differentiation in part by direct interactions with critical components of the release apparatus.…”

Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A)

“…The observation that SV2 binds the extracellular matrix protein laminin (8) suggested that it could participate in the formation of synapses or the establishment of active zones. To determine whether the reduced neurotransmission in SV2A knockouts is caused by changes in synapse density and͞or morphology, synapses were analyzed at the electron microscopic level.…”

“…The absence of SV2 homologs in yeast suggests that it is not a component of the basic membrane trafficking mechanism and, therefore, may mediate a process unique to regulated secretion. The structure and protein interactions of SV2 suggest multiple possible functions, which include acting as a transporter (3)(4)(5), providing a matrix for neurotransmitter concentration and release (7), acting as a receptor for extracellular matrix proteins (8), and regulating the action of other synaptic proteins (9). To explore the function(s) of SV2 in an in vivo context, we used the technique of targeted gene disruption to produce animals that do not express SV2A.…”