Liprin-α2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission

Spangler, Samantha A.; Schmitz, Sabine; Kevenaar, Josta T.; Graaff, Esther de; Wit, Heidi de; Demmers, Jeroen; Toonen, Ruud F.; Hoogenraad, Casper C.

doi:10.1083/jcb.201301011

Cited by 100 publications

(105 citation statements)

References 54 publications

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“…The vertebrate synapse, similar to that at the Drosophila NMJ, exhibits plasticity and our expectation is that MAGUKs that link synaptic junctional proteins to the cytoskeleton show dynamic behavior. Consistent with this, the MAGUK CASK, which links neurexins and the IgCAM SynCAM1 to the cytoskeleton, is mobile at the presynapse in FRAP studies (Biederer et al, 2002;Hata et al, 1996;Spangler et al, 2013). Interestingly, there are results suggesting that the plasticity of a synapse can vary during development as a result of the MAGUK being involved.…”

Section: The Septate Junction and Its Originssupporting

confidence: 60%

Making the connection – shared molecular machinery and evolutionary links underlie the formation and plasticity of occluding junctions and synapses

Harden

Wang

Krieger

2016

Journal of Cell Science

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The pleated septate junction ( pSJ), an ancient structure for cell-cell contact in invertebrate epithelia, has protein components that are found in three more-recent junctional structures, the neuronal synapse, the paranodal region of the myelinated axon and the vertebrate epithelial tight junction. These more-recent structures appear to have evolved through alterations of the ancestral septate junction. During its formation in the developing animal, the pSJ exhibits plasticity, although the final structure is extremely robust. Similar to the immature pSJ, the synapse and tight junctions both exhibit plasticity, and we consider evidence that this plasticity comes at least in part from the interaction of members of the immunoglobulin cell adhesion molecule superfamily with highly regulated membraneassociated guanylate kinases. This plasticity regulation probably arose in order to modulate the ancestral pSJ and is maintained in the derived structures; we suggest that it would be beneficial when studying plasticity of one of these structures to consider the literature on the others. Finally, looking beyond the junctions, we highlight parallels between epithelial and synaptic membranes, which both show a polarized distribution of many of the same proteins -evidence that determinants of apicobasal polarity in epithelia also participate in patterning of the synapse.

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Section: The Septate Junction and Its Originssupporting

confidence: 60%

Making the connection – shared molecular machinery and evolutionary links underlie the formation and plasticity of occluding junctions and synapses

Harden

Wang

Krieger

2016

Journal of Cell Science

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“…Although this study focused on CPX, a large number of other synaptic proteins are subject to diffusive redistribution along the axonal compartment over time. Not all synaptic proteins are anchored to the same extent and a wide variety of mobility values or immobile fractions have been reported on several presynaptic proteins (62,(64)(65)(66)(67)(68)(69). Further studies will be required to determine whether some of the unanchored proteins play a preferential role in use-dependent plasticity because they will have a larger capacity to collect or disperse from individual boutons during ongoing synaptic activity.…”

Section: Implications For Use-dependence Plasticitymentioning

confidence: 94%

Synaptic Activity Regulates the Abundance and Binding of Complexin

Wragg

Gouzer

Bai

et al. 2015

Biophysical Journal

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Nervous system function relies on precise chemical communication between neurons at specialized junctions known as synapses. Complexin (CPX) is one of a small number of cytoplasmic proteins that are indispensable in controlling neurotransmitter release through SNARE and synaptic vesicle interactions. However, the mechanisms that recruit and stabilize CPX are poorly understood. The mobility of CPX tagged with photoactivatable green fluorescent protein (pGFP) was quantified in vivo using Caenorhabditis elegans. Although pGFP escaped the synapse within seconds, CPX-pGFP displayed both fast and slow decay components, requiring minutes for complete exchange of the synaptic pool. The longer synaptic residence time of CPX arose from both synaptic vesicle and SNARE interactions, and surprisingly, CPX mobility depended on synaptic activity. Moreover, mouse CPX-GFP reversibly dispersed out of hippocampal presynaptic terminals during stimulation, and blockade of vesicle fusion prevented CPX dispersion. Hence, synaptic CPX can rapidly redistribute and this exchange is influenced by neuronal activity, potentially contributing to use-dependent plasticity.

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“…The functional implication of this interaction has yet to be elucidated. Recently, liprin-α2, which is required for regulating synaptic vesicle pool size, has been shown to be critical for recruitment of several components of the vesicle release machinery, including CASK (Spangler et al, 2013). …”

Section: Genes Linked To Id and Asdmentioning

confidence: 99%

Intellectual disability and autism spectrum disorders: Causal genes and molecular mechanisms

Srivastava

Schwartz

2014

Neuroscience & Biobehavioral Reviews

179

153

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Intellectual disability (ID) and Autism Spectrum disorder (ASD) are the most common developmental disorders present in humans. Combined, they affect between 3-5% of the population. Additionally, they can be found together in the same individual thereby complicating treatment. The causative factors (genes, epigenetic and environmental) are quite varied and likely interact so as to further complicate the assessment of an individual patient. Nonetheless, much valuable information has been gained by identifying candidate genes for ID or ASD. Understanding the etiology of either ID or ASD is of utmost importance for families. It allows a determination of the risk of recurrence, the possibility of other comorbidity medical problems, the molecular and cellular nature of the pathobiology and hopefully potential therapeutic approaches.

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Liprin-α2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission

Abstract: Liprin-α2 is required for the presynaptic recruitment and turnover of RIM1 and CASK, components of the release machinery, and facilitates synaptic output by regulating synaptic vesicle pool size.

Cited by 100 publications

References 54 publications

Making the connection – shared molecular machinery and evolutionary links underlie the formation and plasticity of occluding junctions and synapses

Making the connection – shared molecular machinery and evolutionary links underlie the formation and plasticity of occluding junctions and synapses

Synaptic Activity Regulates the Abundance and Binding of Complexin

Intellectual disability and autism spectrum disorders: Causal genes and molecular mechanisms

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