CaMKII in neuronal development
Location
Georgia
Start Date
12-5-2015 1:00 PM
Description
Genes associated with mental retardation and autism are intricately involved in mediating neuronal communication either by a role in neuronal maturation, connectivity, synaptic function, balancing neuronal excitability, or mediating activity-initiated changes in neuronal function. CaMKII has a role in all of these events. CaMKII is a predominant protein in the adult brain comprising 1~2% of the total protein in neurons. CaMKIIa and b are the two major isoforms in the brain and hetero- and homo-oligomerize to form the CaMKII multimeric enzyme. CaMKII isoforms share 80~90% sequence homology. A variable domain of CaMKII contributes to the uniqueness of each isoform. Alternative splicing within this domain generates CaMKII isoform splice variants that differ in subcellular localization and function. CaMKIIb is alternatively spliced within the variable domain to generate four splice variants (b, b’, be, b’e). The CaMKIIb variant contains the full-length variable domain and, unlike CaMKIIa, has the ability to interact with F-actin. The interaction of CaMKIIb with F-actin has been shown to have a role in formation of filopodia, dendrite spines, and synapses (Fink et al. 2003). How the alternative spliced forms of CaMKIIb contribute to CaMKII function in neuronal development is unclear. To investigate the potential role of CaMKIIb association with F-actin in developing neurons, we identified a novel F-actin rich structure, we termed “microspike”, in embryonic cortical neurons. In this study, we took advantage of the temporal and spatial regulation of CaMKII isoform expression to unveil a role for CaMKIIb in F-actin binding and stability.
CaMKII in neuronal development
Georgia
Genes associated with mental retardation and autism are intricately involved in mediating neuronal communication either by a role in neuronal maturation, connectivity, synaptic function, balancing neuronal excitability, or mediating activity-initiated changes in neuronal function. CaMKII has a role in all of these events. CaMKII is a predominant protein in the adult brain comprising 1~2% of the total protein in neurons. CaMKIIa and b are the two major isoforms in the brain and hetero- and homo-oligomerize to form the CaMKII multimeric enzyme. CaMKII isoforms share 80~90% sequence homology. A variable domain of CaMKII contributes to the uniqueness of each isoform. Alternative splicing within this domain generates CaMKII isoform splice variants that differ in subcellular localization and function. CaMKIIb is alternatively spliced within the variable domain to generate four splice variants (b, b’, be, b’e). The CaMKIIb variant contains the full-length variable domain and, unlike CaMKIIa, has the ability to interact with F-actin. The interaction of CaMKIIb with F-actin has been shown to have a role in formation of filopodia, dendrite spines, and synapses (Fink et al. 2003). How the alternative spliced forms of CaMKIIb contribute to CaMKII function in neuronal development is unclear. To investigate the potential role of CaMKIIb association with F-actin in developing neurons, we identified a novel F-actin rich structure, we termed “microspike”, in embryonic cortical neurons. In this study, we took advantage of the temporal and spatial regulation of CaMKII isoform expression to unveil a role for CaMKIIb in F-actin binding and stability.