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The Nebulin Family LIM and SH3 Proteins Regulate Postsynaptic Development and Function
- Source :
- J Neurosci
- Publication Year :
- 2020
- Publisher :
- Society for Neuroscience, 2020.
-
Abstract
- Neuronal dendrites have specialized actin-rich structures called dendritic spines that receive and integrate most excitatory synaptic inputs. The stabilization of dendrites and spines during neuronal maturation is essential for proper neural circuit formation. Changes in dendritic morphology and stability are largely mediated by regulation of the actin cytoskeleton; however, the underlying mechanisms remain to be fully elucidated. Here, we present evidence that the nebulin family members LASP1 and LASP2 play an important role in the postsynaptic development of rat hippocampal neurons from both sexes. We find that both LASP1 and LASP2 are enriched in dendritic spines, and their knockdown impairs spine development and synapse formation. Furthermore, LASP2 exerts a distinct role in dendritic arbor and dendritic spine stabilization. Importantly, the actin-binding N-terminal LIM domain and nebulin repeats of LASP2 are required for spine stability and dendritic arbor complexity. These findings identify LASP1 and LASP2 as novel regulators of neuronal circuitry.SIGNIFICANCE STATEMENTProper regulation of the actin cytoskeleton is essential for the structural stability of dendrites and dendritic spines. Consequently, the malformation of dendritic structures accompanies numerous neurologic disorders, such as schizophrenia and autism. Nebulin family members are best known for their role in regulating the stabilization and function of actin thin filaments in muscle. The two smallest family members, LASP1 and LASP2, are more structurally diverse and are expressed in a broader array of tissues. While both LASP1 and LASP2 are highly expressed in the brain, little is currently known about their function in the nervous system. In this study, we demonstrate the first evidence that LASP1 and LASP2 are involved in the formation and long-term maintenance of dendrites and dendritic spines.
- Subjects :
- 0301 basic medicine
Dendritic spine
Patch-Clamp Techniques
Dendritic Spines
Muscle Proteins
Dendrite
Nerve Tissue Proteins
Biology
Hippocampus
Synapse
src Homology Domains
03 medical and health sciences
Nebulin
0302 clinical medicine
Postsynaptic potential
medicine
Animals
Actin
Research Articles
LIM domain
Neurons
General Neuroscience
Microfilament Proteins
Excitatory Postsynaptic Potentials
Dendrites
LIM Domain Proteins
Actin cytoskeleton
Actins
Rats
030104 developmental biology
medicine.anatomical_structure
Gene Knockdown Techniques
biology.protein
Nerve Net
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Neurosci
- Accession number :
- edsair.doi.dedup.....80ba62985a3f2145ec24c8cbab46ac07