Regulation of Dendritic Spine Morphology and Synaptic Function by Shank and Homer

Sala, Carlo; Piëch, Valentin; Wilson, Nathan R.; Passafaro, Maria; Liu, Guosong; Sheng, Morgan

doi:10.1016/s0896-6273(01)00339-7

Cited by 638 publications

(635 citation statements)

References 50 publications

(4 reference statements)

Supporting

Mentioning

591

Contrasting

Unclassified

Order By: Relevance

“…Dendritic spines were classified according the following parameters: mushroom (length ≤ 1.2 μm, width Z0.5 μm); filopodia (length 41.2 μm, width o0.5 μm), in line with. 65 Colocalization of two or three selected markers was measured using the boolean function 'AND' for the selected channels. The resulting image was binarized and used as a colocalization mask to be subtracted to single channels.…”

Section: Methodsmentioning

confidence: 99%

Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis

et al. 2015

View full text Add to dashboard Cite

Impairment of synaptic function can lead to neuropsychiatric disorders collectively referred to as synaptopathies. The SNARE protein SNAP-25 is implicated in several brain pathologies and, indeed, brain areas of psychiatric patients often display reduced SNAP-25 expression. It has been recently found that acute downregulation of SNAP-25 in brain slices impairs long-term potentiation; however, the processes through which this occurs are still poorly defined. We show that in vivo acute downregulation of SNAP-25 in CA1 hippocampal region affects spine number. Consistently, hippocampal neurons from SNAP-25 heterozygous mice show reduced densities of dendritic spines and defective PSD-95 dynamics. Finally, we show that, in brain, SNAP-25 is part of a molecular complex including PSD-95 and p140Cap, with p140Cap being capable to bind to both SNAP-25 and PSD-95. These data demonstrate an unexpected role of SNAP-25 in controlling PSD-95 clustering and open the possibility that genetic reductions of the protein levels -as occurring in schizophrenia -may contribute to the pathology through an effect on postsynaptic function and plasticity. Cell Death and Differentiation (2015) 22, 1425-1436 doi:10.1038/cdd.2014 published online 13 February 2015 Synapses are complex cellular junctions specialized for communication between neurons. Epidemiological and genetic studies demonstrated that deficiencies in synapse function 1 are implicated in a wide range of brain disorders, including neurodegenerative 2 and psychiatric diseases such as schizophrenia 3,4 and autism. 5,6 A hallmark of synaptic specializations is their dependence on highly organized complexes of proteins that interact with each other. Therefore, the loss or modification of key synaptic proteins might directly affect the properties of such networks and, ultimately, synaptic function.SNAP-25 is a component of the SNARE complex, which is central to synaptic vesicle exocytosis 7,8 and which has a role in the regulation of voltage-gated calcium channels. 9,10 The SNAP25 gene has been associated with attention deficit hyperactivity disorder (ADHD) 11,12 and with schizophrenia. 13,14 Consistently, SNAP-25 levels are lower in the hippocampus 15 and in the frontal lobe 16 of patients with schizophrenia. DNA variants of the SNAP25 gene that associate with ADHD are also associated with reduced expression level of the transcript in prefrontal cortex. 17 Finally, reduction of SNAP-25 levels has been found to cause neurodegeneration in mice lacking the synaptic vesicle protein Cysteine-string protein-α, possibly due to the impaired SNARE-complex assembly produced by the decreased SNAP-25. 18 The mechanisms by which reduced SNAP-25 expression may result in a psychiatric disease are still undefined, although alterations in neurotransmitter release have been indicated as potential causative processes. 19,20 Recently an unexpected postsynaptic role of SNAP-25 has been described, with the protein controlling NMDA and kainate receptor trafficking. 21 Furthermore, it has been lately ...

show abstract

Section: Methodsmentioning

confidence: 99%

Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In general, SHANK1 promotes dendritic spine head enlargement, and SHANK2 and 3 promote dendritic spine formation, with SHANK3 also inhibiting dendritic spine arborization by binding to Densin-180 [173][174][175][176][177] . Shank3 knockout mice suffer from a loss of cortical actin filaments, in association with reduced Rac1/p21-activated kinase (PAK) activity together with increased activity of cofilin 178 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

“…This analysis was performed in neurons at DIV 12-14, a period where spines begin to emerge. Changes in the relative proportions of filopodia and spines were contrasted to Shank1b, a potent modulator of spine maturation (Sala et al, 2001). Because the palmitoylation motif of paralemmin-1 fused to GFP (paralemmin CT) is sufficient to increase the number of filopodia in neuronal cells ( Figure 2B), we first examined whether paralemmin-CT induced filopodia is sufficient to increase spine number.…”

Section: Spine Induction By Paralemmin-1 Is Regulated By Alternative mentioning

confidence: 99%

Paralemmin-1, a Modulator of Filopodia Induction Is Required for Spine Maturation

Arstikaitis

Gauthier-Campbell

Herrera

et al. 2008

MBoC

Self Cite

View full text Add to dashboard Cite

Dendritic filopodia are thought to participate in neuronal contact formation and development of dendritic spines; however, molecules that regulate filopodia extension and their maturation to spines remain largely unknown. Here we identify paralemmin-1 as a regulator of filopodia induction and spine maturation. Paralemmin-1 localizes to dendritic membranes, and its ability to induce filopodia and recruit synaptic elements to contact sites requires protein acylation. Effects of paralemmin-1 on synapse maturation are modulated by alternative splicing that regulates spine formation and recruitment of AMPA-type glutamate receptors. Paralemmin-1 enrichment at the plasma membrane is subject to rapid changes in neuronal excitability, and this process controls neuronal activity-driven effects on protrusion expansion. Knockdown of paralemmin-1 in developing neurons reduces the number of filopodia and spines formed and diminishes the effects of Shank1b on the transformation of existing filopodia into spines. Our study identifies a key role for paralemmin-1 in spine maturation through modulation of filopodia induction. INTRODUCTIONDuring CNS excitatory synapse development, the formation of spines, bulbous protrusions enriched with F-actin, is essential for proper synaptic transmission and neuronal function (Hall and Nobes, 2000;Yuste and Bonhoeffer, 2004;Halpain et al., 2005;Matus, 2005;. Spines contain a plethora of proteins including neurotransmitter receptors, cytoskeleton-associated proteins, and cell adhesion molecules. Spines are pleomorphic protrusions that can be modified by changes in neuronal activity, which regulate actin-based motility (Fischer et al., 1998;Portera-Cailliau et al., 2003;Matus, 2005). Defects in spine maturation and function have been associated with several forms of mental retardation including Down, Rett, Fragile X, and fetal alcohol syndromes. Some of these disorders exhibit a reduction in spine size and density and the formation of long, thin filopodia-like structures (Hering and Sheng, 2001;Zoghbi, 2003).Although our knowledge of molecules that control the morphology and functional properties of dendritic spines has expanded, information about the structures from which spines emerge is lacking. Dendritic filopodia, thin protrusions ranging in length from 2 to 35 m, are thought to participate in synaptogenesis, dendritic branching and the development of spines. During synaptogenesis, filopodia decorate the dendrites of neurons. Studies show that dendritic filopodia exhibit highly dynamic protrusive motility during periods of active synaptogenesis (Dailey and Smith, 1996;Ziv and Smith, 1996;Marrs et al., 2001). Thus, filopodia are thought to function by extending and probing the environment for appropriate presynaptic partners, thereby aiding in synapse formation. These results are further supported by electron microscopy studies which show that synapses can be formed at the tip and base of dendritic filopodia (Fiala et al., 1998;Kirov et al., 2004). As synapses form, the number of filopodia d...

show abstract

Regulation of Dendritic Spine Morphology and Synaptic Function by Shank and Homer

Cited by 638 publications

References 50 publications

Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis

Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis

Dendritic spine actin cytoskeleton in autism spectrum disorder

Paralemmin-1, a Modulator of Filopodia Induction Is Required for Spine Maturation

Contact Info

Product

Resources

About