The actin cytoskeleton in presynaptic assembly

Nelson, Jessica C.; Stavoe, Andrea K.H.; Colón-Ramos, Daniel A.

doi:10.4161/cam.24803

Cited by 62 publications

(50 citation statements)

References 95 publications

(140 reference statements)

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“…In nonneuronal cells, interaction of SPARC with β1 integrin complexes linked to cytoskeletal proteins, such as talin and actin, mediates the loss of focal adhesions (24,31,33). In vitro results using jasplakinolide suggest an analogous mechanism in synapses, through which depolymerization of synaptic F-actin cytoskeleton may lead to disruption of active zones and disorganization of synaptic vesicle pools (34,35). The resulting presynaptic endosomal structures could be digested within neurons; however, it is possible that in vivo activation of same program would ultimately involve phagocytosis by glial cells, i.e., axosome shedding (2).…”

Section: Discussionmentioning

confidence: 99%

SPARC triggers a cell-autonomous program of synapse elimination

López-Murcia

Terni

Llobet

2015

Proc. Natl. Acad. Sci. U.S.A.

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Elimination of the excess synaptic contacts established in the early stages of neuronal development is required to refine the function of neuronal circuits. Here we investigate whether secreted protein acidic and rich in cysteine (SPARC), a molecule produced by glial cells, is involved in synapse removal. SPARC production peaks when innervation of the rat superior cervical ganglion and the tail of Xenopus tropicalis tadpoles are remodeled. The formation of new cholinergic synapses in autaptic single-cell microcultures is inhibited by SPARC. The effect resides in the C-terminal domain, which is also responsible for triggering a concentration-and time-dependent disassembly of stable cholinergic synapses. The loss of synaptic contacts is associated with the formation of retracted axon terminals containing multivesicular bodies and secondary lysosomes. The biological relevance of in vitro results was supported by injecting the tail of Xenopus tropicalis tadpoles with peptide 4.2, a 20-aa sequence derived from SPARC that mimics full-length protein effects. Swimming was severely impaired at ∼5 h after peptide application, caused by the massive elimination of neuromuscular junctions and pruning of axonal branches. Effects revert by 6 d after injection, as motor innervation reforms. In conclusion, SPARC triggers a cell-autonomous program of synapse elimination in cholinergic neurons that likely occurs when protein production peaks during normal development.neuron-glia interaction | synapse elimination | SPARC | Xenopus tropicalis | cholinergic synapse

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Section: Discussionmentioning

confidence: 99%

SPARC triggers a cell-autonomous program of synapse elimination

López-Murcia

Terni

Llobet

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The fusion of SVs with the active zone membrane is followed by SV recycling through endocytosis 213,214 . Actin is abundant in the presynapses and performs active roles in vesicle trafficking and the development of presynaptic terminals 203,215 . Actin interaction with synapsin, which is phosphorylated upon neuronal activity is crucial for the organization of the SV pools within the presynaptic nerve A C C E P T E D M A N U S C R I P T …”

Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Superresolution microscopy has shown that bassoon but not piccolo colocalises with VGCCs (Nishimune et al, 2016); this spatial separation suggests different interacting partners, and that bassoon localisation might rely on VGCCs when integrin-α3 is disrupted. Interestingly, integrins associate with actin, which has also been implicated in AZ assembly at central synapses, via interactions with bassoon, piccolo and other components (Nelson et al, 2013). Therefore, the modulation of actin dynamics might be a potential mechanism through which integrin-α3 regulates AZ composition.…”

Section: Role Of Integrin-α3 At the Azmentioning

confidence: 99%

Multiple roles of integrin-α3 at the neuromuscular junction

Ross

Webster

Lechertier

et al. 2017

Journal of Cell Science

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The neuromuscular junction (NMJ) is the synapse between motoneurons and skeletal muscle, and is responsible for eliciting muscle contraction. Neurotransmission at synapses depends on the release of synaptic vesicles at sites called active zones (AZs). Various proteins of the extracellular matrix are crucial for NMJ development; however, little is known about the identity and functions of the receptors that mediate their effects. Using genetically modified mice, we find that integrin-α3 (encoded by Itga3), an adhesion receptor at the presynaptic membrane, is involved in the localisation of AZ components and efficient synaptic vesicle release. Integrin-α3 also regulates integrity of the synapse -mutant NMJs present with progressive structural changes and upregulated autophagy, features commonly observed during ageing and in models of neurodegeneration. Unexpectedly, we find instances of nerve terminal detachment from the muscle fibre; to our knowledge, this is the first report of a receptor that is required for the physical anchorage of pre-and postsynaptic elements at the NMJ. These results demonstrate multiple roles of integrin-α3 at the NMJ, and suggest that alterations in its function could underlie defects that occur in neurodegeneration or ageing.

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The actin cytoskeleton in presynaptic assembly

Cited by 62 publications

References 95 publications

SPARC triggers a cell-autonomous program of synapse elimination

SPARC triggers a cell-autonomous program of synapse elimination

Dendritic spine actin cytoskeleton in autism spectrum disorder

Multiple roles of integrin-α3 at the neuromuscular junction

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