title: Neurolastin, a Dynamin Family GTPase, Regulates Excitatory Synapses and Spine Density.
abstract: Membrane trafficking and spinogenesis contribute significantly to changes in synaptic strength during development and in various paradigms of synaptic plasticity. GTPases of the dynamin family are key players regulating membrane trafficking. Here, we identify a brain-specific dynamin family GTPase, neurolastin (RNF112/Znf179), with closest homology to atlastin. We demonstrate that neurolastin has functional GTPase and RING domains, making it a unique protein identified with this multi-enzymatic domain organization. We also show that neurolastin is a peripheral membrane protein that localizes to endosomes and affects endosomal membrane dynamics via its RING domain. In addition, neurolastin knockout mice have fewer dendritic spines, and rescue of the wild-type phenotype requires both the GTPase and RING domains. Furthermore, we find fewer functional synapses and reduced paired pulse facilitation in neurolastin knockout mice. Thus, we identify neurolastin as a dynamin family GTPase that affects endosome size and spine density.
authors.affiliation: Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA.
authors.forename: Richa Madan
authors.initials: RM
authors.lastname: Lomash
authors.affiliation: Synapse and Neural Circuit Research Unit, NINDS, NIH, Bethesda, MD 20892, USA.
authors.forename: Xinglong
authors.initials: X
authors.lastname: Gu
authors.affiliation: Surgical Neurology Branch, NINDS, NIH, Bethesda, MD 20892, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Youle
authors.affiliation: Synapse and Neural Circuit Research Unit, NINDS, NIH, Bethesda, MD 20892, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA. Electronic address: rochek@ninds.nih.gov.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Roche
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D034281:Dynamins