The Ras-like GTPase Rem2 is a potent inhibitor of calcium/calmodulin-dependent kinase II activity.

Ca/calmodulin-dependent protein kinase II (CaMKII) is a well-characterized, abundant protein kinase that regulates a diverse set of functions in a tissue-specific manner. For example, in heart muscle, CaMKII regulates Ca homeostasis, whereas in neurons, CaMKII regulates activity-dependent dendritic remodeling and long-term potentiation (LTP), a neurobiological correlate of learning and memory. Previously, we identified the GTPase Rem2 as a critical regulator of dendrite branching and homeostatic plasticity in the vertebrate nervous system.

Rem2 signaling affects neuronal structure and function in part by regulation of gene expression.

The central nervous system has the remarkable ability to convert changes in the environment in the form of sensory experience into long-term alterations in synaptic connections and dendritic arborization, in part through changes in gene expression. Surprisingly, the molecular mechanisms that translate neuronal activity into changes in neuronal connectivity and morphology remain elusive. Rem2, a member of the Rad/Rem/Rem2/Gem/Kir (RGK) subfamily of small Ras-like GTPases, is a positive regulator of synapse formation and negative regulator of dendritic arborization.

Accelerated actin filament polymerization from microtubule plus ends.

Microtubules (MTs) govern actin network remodeling in a wide range of biological processes, yet the mechanisms underlying this cytoskeletal cross-talk have remained obscure. We used single-molecule fluorescence microscopy to show that the MT plus-end-associated protein CLIP-170 binds tightly to formins to accelerate actin filament elongation. Furthermore, we observed mDia1 dimers and CLIP-170 dimers cotracking growing filament ends for several minutes.

CaMKII-dependent phosphorylation of the GTPase Rem2 is required to restrict dendritic complexity.

The morphogenesis of the dendritic arbor is a critical aspect of neuronal development, ensuring that proper neural networks are formed. However, the molecular mechanisms that underlie this dendritic remodeling remain obscure. We previously established the activity-regulated GTPase Rem2 as a negative regulator of dendritic complexity.

Distinct Kinesin-14 mitotic mechanisms in spindle bipolarity.

Kinesin-like proteins are integral to formation and function of a conserved mitotic spindle apparatus that directs chromosome segregation and precedes cell division. Ubiquitous to the mechanism of spindle assembly and stability are balanced Kinesin-5 promoting and Kinesin-14 opposing forces. Distinct Kinesin-14 roles in bipolarity in eukaryotes have not been shown, but are suggested by gamma-tubulin-based pole interactions that affect establishment and by microtubule cross-linking and sliding that maintain bipolarity and spindle length.