title: Neurabins recruit protein phosphatase-1 and inhibitor-2 to the actin cytoskeleton.
abstract: Inhibitor-2 (I-2) bound protein phosphatase-1 (PP1) and several PP1-binding proteins from rat brain extracts, including the actin-binding proteins, neurabin I and neurabin II. Neurabins from rat brain lysates were sedimented by I-2 and its structural homologue, I-4. The central domain of both neurabins bound PP1 and I-2, and mutation of a conserved PP1-binding motif abolished neurabin binding to both proteins. Microcystin-LR, a PP1 inhibitor, also attenuated I-2 binding to neurabins. Immunoprecipitation of neurabin I established its association with PP1 and I-2 in HEK293T cells and suggested that PP1 mediated I-2 binding to neurabins. The C terminus of I-2, although not required for PP1 binding, facilitated PP1 recruitment by neurabins, which also targeted I-2 to polymerized F-actin. Mutations that attenuated PP1 binding to I-2 and neurabin I suggested distinct and overlapping sites for these two proteins on the PP1 catalytic subunit. Immunocytochemistry in epithelial cells and cultured hippocampal neurons showed that endogenous neurabin II and I-2 colocalized at actin-rich structures, consistent with the ability of neurabins to target the PP1.I-2 complex to actin cytoskeleton and regulate cell morphology.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Terry-Lorenzo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Elliot
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Weiser
authors.forename: Todd D
authors.initials: TD
authors.lastname: Prickett
authors.forename: David L
authors.initials: DL
authors.lastname: Brautigan
authors.forename: Shirish
authors.initials: S
authors.lastname: Shenolikar
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D020134:Catalytic Domain; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone; D003599:Cytoskeleton / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D056488:Histone Chaperones; D006801:Humans; D007150:Immunohistochemistry; D008387:Marine Toxins; D052998:Microcystins; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D054645:Protein Phosphatase 1; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors; D000099273:Neurabins
chemical_list: D000199:Actins; D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D008387:Marine Toxins; D052998:Microcystins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010456:Peptides, Cyclic; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D011506:Proteins; D014157:Transcription Factors; D000099273:Neurabins; C513473:SET protein, human; C057862:cyanoginosin LR