Neuron-enriched phosphatase and actin regulator 3 (Phactr3)/ nuclear scaffold-associated PP1-inhibiting protein (Scapinin) regulates dendritic morphology via its protein phosphatase 1-binding domain

Biochem Biophys Res Commun. 2020 Jul 23;528(2):322-329. doi: 10.1016/j.bbrc.2020.05.006. Epub 2020 May 15.

Abstract

Phosphatase and actin regulator 3/nuclear scaffold-associated protein phosphatase 1-inhibiting protein (Phactr3/Scapinin) is an actin- and protein phosphatase 1 (PP1)-binding protein known to negatively regulate axon elongation. In this study, we examined the expression pattern of Phactr3/Scapinin in several tissues and investigated the effect of Phactr3/Scapinin on dendritic morphology of cortical neurons. Results showed that Phactr3/Scapinin expression was up-regulated in the developing brain and enriched in neurons and in the postsynaptic density fraction, but not in astrocytes. Overexpression of wild type or mutant Phactr3/Scapinin, which lacked actin-binding activity, resulted in increased dendritic complexity and percentage of spines with a mushroom or stubby shape, as well as a decrease in spine density. However, overexpression of mutant Phactr3/Scapinin that lacked PP1-binding activity did not. Taken together, these findings suggest that Phactr3/Scapinin expression is neuronal and might contribute to synaptic formation via distinct actin- and PP1-binding domains involved in dendritic and axonal morphology, respectively.

Keywords: Actin; Dendrite; Dendritic spine; Nuclear scaffold-associated PP1-Inhibiting protein; Phosphatase and actin regulator; Protein phosphatase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / cytology
  • Dendrites / metabolism*
  • Female
  • Male
  • Mice, Inbred C57BL
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / metabolism*
  • Mutation / genetics
  • Nuclear Matrix / metabolism*
  • Nuclear Matrix-Associated Proteins / chemistry*
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Domains
  • Protein Phosphatase 1 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Subcellular Fractions / metabolism
  • Up-Regulation / genetics

Substances

  • Microfilament Proteins
  • Nuclear Matrix-Associated Proteins
  • Nuclear Proteins
  • Phactr3 protein, rat
  • RNA, Messenger
  • scapinin protein, mouse
  • Protein Phosphatase 1