Neurabin: A Novel Neural Tissue–specific Actin Filament–binding Protein Involved in Neurite Formation

Abstract

We purified from rat brain a novel actin filament (F-actin)–binding protein of ∼180 kD (p180), which was specifically expressed in neural tissue. We named p180 neurabin (neural tissue–specific F-actin– binding protein). We moreover cloned the cDNA of neurabin from a rat brain cDNA library and characterized native and recombinant proteins. Neurabin was a protein of 1,095 amino acids with a calculated molecular mass of 122,729. Neurabin had one F-actin–binding domain at the NH2-terminal region, one PSD-95, DlgA, ZO-1–like domain at the middle region, a domain known to interact with transmembrane proteins, and domains predicted to form coiled-coil structures at the COOH-terminal region. Neurabin bound along the sides of F-actin and showed F-actin–cross-linking activity. Immunofluorescence microscopic analysis revealed that neurabin was highly concentrated in the synapse of the developed neurons. Neurabin was also concentrated in the lamellipodia of the growth cone during the development of neurons. Moreover, a study on suppression of endogenous neurabin in primary cultured rat hippocampal neurons by treatment with an antisense oligonucleotide showed that neurabin was involved in the neurite formation. Neurabin is a candidate for key molecules in the synapse formation and function.

Brain Actin-associated Protein Phosphatase 1 Holoenzymes Containing Spinophilin, Neurabin, and Selected Catalytic Subunit Isoforms

“…2 In addition, the peptide sequences were 84% identical to portions of neurabin, a spinophilin homolog which was purified as an F-actin-binding protein and cloned (16). The apparent molecular weights of spinophilin and neurabin by SDS-PAGE were noted to be considerably larger than sizes predicted from their amino acid sequences (16,17), but are similar to the apparent molecular weights of PP1bp134 and PP1bp175, respectively. While interaction of PP1 with spinophilin was established previously (14), association of PP1 with neurabin has not been documented.…”

“…The peptides were 100% identical to portions of spinophilin, which was identified as a PP1bp by yeast two-hybrid analysis (14) and was independently purified as an F-actin-binding protein (17). 2 In addition, the peptide sequences were 84% identical to portions of neurabin, a spinophilin homolog which was purified as an F-actin-binding protein and cloned (16). The apparent molecular weights of spinophilin and neurabin by SDS-PAGE were noted to be considerably larger than sizes predicted from their amino acid sequences (16,17), but are similar to the apparent molecular weights of PP1bp134 and PP1bp175, respectively.…”

Regulation and Function of Glycogen Synthase Kinase-3 Isoforms in Neuronal Survival

“…Thus, a reduction in GSK-3 activity results in a decrease in Thr 72 phosphorylation of PP1 inhibitor-2 (and hence, activation of its inhibitory effect), causing suppression of PP1 activity and induction of GSK-3/PP1 inhibitor-2/PP1/GSK-3 autoregulatory circuitry. PP1 has critical roles in neuronal functions, including regulation of neurite formation (59) and modulation of glutamatergic neurotransmission (60) through binding to the scaffold protein neurabin I at different subcellular locations in maturing mammalian neurons (61,62). It is noteworthy that GSK-3 and its inhibition have also been implicated in axonal morphology and synaptic protein clustering in developing neurons (63).…”

Involvement of Cdc42 small G protein in cell-cell adhesion, migration and morphology of MDCK cells

“…At adherens junction, cadherins interact with each other at the extracellular surface and serve as adhesion molecules (for reviews, see Geiger and Ginsberg, 1991;Tsukita et al, 1992;Takeichi, 1995). Cadherins indirectly interact at the cytoplasmic region with the actin cytoskeleton through many peripheral membrane proteins, including a-, b-, and g-catenins, p120, a-actinin, vinculin, neurabin, and afadin (Vestweber and Kemler, 1984;Peyrieras et al, 1985;Ozawa et al, 1989;Shibamoto et al, 1995;Nakanishi et al, 1997;Mandai et al, 1997). Tight junction also plays an important role in the formation of cell polarity and barrier (for reviews, see Schneeberger and Lynch, 1992;Gumbiner, 1993;Anderson and Van Itallie, 1995).…”