Neurolastin, a Dynamin Family GTPase, Regulates Excitatory Synapses and Spine Density

• Neurolastin is a unique dynamin family GTPase with a RING domain
• Neurolastin affects endosome size via its RING domain
• Neurolastin KO mice have decreased spine density and impaired synaptic transmission
• Neurolastin GTPase and RING domains are important for maintenance of spine density

SummaryMembrane 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.

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