High impact information on PPP1R9A

• Neurabin was also concentrated in the lamellipodia of the growth cone during the development of neurons [1].
• Neurabin: a novel neural tissue-specific actin filament-binding protein involved in neurite formation [1].
• We moreover cloned the cDNA of neurabin from a rat brain cDNA library and characterized native and recombinant proteins [1].
• Targeting protein phosphatase 1 (PP1) to the actin cytoskeleton: the neurabin I/PP1 complex regulates cell morphology [2].
• In vitro and in vivo studies suggested that the actin-binding domain attenuated protein kinase A (PKA) phosphorylation of neurabin I [2].

Biological context of PPP1R9A

• Deletion of the C-terminal coiled-coil and sterile alpha motif domains abolished neurabin I dimerization and induced filopodium extension [2].
• Direct interaction of the trans-Golgi network membrane protein, TGN38, with the F-actin binding protein, neurabin [3].
• While wild-type neurabin-I elicited no change in basal synaptic transmission, it enhanced LTD and inhibited LTP in CA1 pyramidal neurons [4].
• Genomic imprinting of PPP1R9A encoding neurabin I in skeletal muscle and extra-embryonic tissues [5].

Anatomical context of PPP1R9A

• Biochemical and cellular studies showed that an N-terminal F-actin-binding domain dictated neurabin I localization at actin cytoskeleton and promoted disassembly of stress fibers [2].
• Mutation of the PP1-binding motif or PP1 inhibition by okadaic acid and calyculin A abolished filopodia and restored stress fibers in cells expressing neurabin I [2].
• TGN38 and neurabin also interact in vivo as demonstrated by coimmunoprecipitation from stably transfected PC12 cells [3].
• In addition, they impaired the ability of PP1 to bind neurabin-I, the neuronal regulatory subunit, and G(M), the skeletal muscle glycogen-targeting subunit [6].
• The neuron-specific actin-binding protein, neurabin-I, is enriched in dendritic spines, and tethers PP1 to actin-rich postsynaptic density to regulate morphology and maturation of spines [4].

Other interactions of PPP1R9A

• These included MAGI-2, MAGI-3 and neurabin [7].

Analytical, diagnostic and therapeutic context of PPP1R9A

• Immunofluorescence microscopic analysis revealed that neurabin was highly concentrated in the synapse of the developed neurons [1].
• Neurabin I interacted with PP1alpha in an overlay assay, in yeast two-hybrid interaction analysis, and in coprecipitation and co-immunoprecipitation experiments [8].

References