title: Regulation of synapse structure and function by distinct myosin II motors.
abstract: Ongoing synaptic function and rapid, bidirectional plasticity are both controlled by regulatory mechanisms within dendritic spines. Spine actin dynamics maintain synapse structure and function, and cytoskeletal rearrangements in these structures trigger structural and functional plasticity. Therefore, proteins that interact with actin filaments are attractive candidates to regulate synaptic actin dynamics and, thus, synapse structure and function. Here, we have cloned the rat isoform of class II myosin heavy chain MyH7B in brain. Unexpectedly, this isoform resembles muscle-type myosin II rather than the ubiquitously expressed nonmuscle myosin II isoforms, suggesting that a rich functional diversity of myosin II motors may exist in neurons. Indeed, reducing the expression of MyH7B in mature neurons caused profound alterations to dendritic spine structure and excitatory synaptic strength. Structurally, dendritic spines had large, irregularly shaped heads that contained many filopodia-like protrusions. Neurons with reduced MyH7B expression also had impaired miniature EPSC amplitudes accompanied by a decrease in synaptic AMPA receptors, which was linked to alterations of the actin cytoskeleton. MyH7B-mediated control over spine morphology and synaptic strength was distinct from that of a nonmuscle myosin, myosin IIb. Interestingly, when myosin IIb expression and MyH7B expression were simultaneously knocked-down in neurons, a third, more pronounced phenotype emerged. Together, our data provide evidence that distinct myosin II isoforms work together to regulate synapse structure and function in cultured hippocampal neurons. Thus, myosin II motor activity is emerging as a broad regulatory mechanism for control over complex actin networks within dendritic spines.
authors.affiliation: Department of Neurobiology, University of Alabama, Birmingham, AL 35294, USA.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Rubio
authors.forename: Richard
authors.initials: R
authors.lastname: Johnson
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Miller
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Gavin
authors.initials: G
authors.lastname: Rumbaugh
mesh_terms: D000199:Actins / Q000648:ultrastructure; D000818:Animals; D024722:Cardiac Myosins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008297:Male; D055369:Miniature Postsynaptic Potentials; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D024501:Nonmuscle Myosin Type IIB / Q000096:biosynthesis; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D000199:Actins; C556964:MyH7B protein, rat; D020033:Protein Isoforms; D018091:Receptors, AMPA; D024722:Cardiac Myosins; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains