1: Regulation of spinogenesis in mature Purkinje cells via mGluR/PKC-mediated phosphorylation of CaMKII beta

Science of the Month - September 2017

PNAS

114 (26):E5256-E5265; 10.1073/pnas.1617270114 JUN 27 2017

Sugawara, Takeyuki; Hisatsune, Chihiro; Miyamoto, Hiroyuki; Ogawa, Naoko; Mikoshiba, Katsuhiko

From left: Katsuhiko Mikoshiba, Takeyuki Sugawara (first author), Chihiro Hisatsune (second author)

In our brains, functional neural circuits are constructed by the precise connection of a vast number of neurons. The dendrites of neurons have countless small protrusions called spines, where synapses, the junctions between neurons, are formed. In recent years, the association between various psychiatric disorders and abnormalities in neuronal spines has been gaining attention. However, how the number and shape of spines are regulated was not yet well understood.

In this study, we discovered that a protein called calcium/calmodulin-dependent protein kinase II beta subunit (CaMKIIβ) regulates the number and shape of spines in Purkinje cells, which are neurons in the cerebellum responsible for motor learning. Furthermore, upon detailed investigation of its mechanism, we found that this function of CaMKIIβ on spines is regulated by phosphorylation by protein kinase C (PKC), a type of protein phosphorylating enzyme. In other words, the phosphorylation of CaMKIIβ by PKC plays a crucial role in correctly regulating the number and shape of spines in Purkinje cells.

This achievement is expected to lead to the elucidation of the causes of various psychiatric disorders and the establishment of therapeutic methods.

This discovery was prompted by the analysis of IP3 receptor type 1-deficient mice. In mice deficient in this receptor only in the Purkinje cells of the mature cerebellum, the number and height of spines increased, and the learning function of the cerebellum (long-term depression) was suppressed. This provided a clue, leading us to search for downstream molecules of the IP3 receptor type 1, which ultimately led us to CaMKIIβ.

(Senior Team Leader, Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute

Katsuhiko Mikoshiba, Class of 1972)

Other Published Papers

1: Are ILC2s Jekyll and Hyde in airway inflammation?

IMMUNOLOGICAL REVIEWS

278 (1):207-218; SI 10.1111/imr.12547 JUL 2017

Ealey, Kafi N.; Moro, Kazuyo; Koyasu, Shigeo

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1: Organoid Transplantation Improves Survival in Short Bowel Syndrome Models by Providing Bile Acid Absorption Function / 2: Rethinking the Value of Atrial Fibrillation Screening — What Risks Should Be Targeted?

1: Development of a Method to Restore the Function of Lost Genes in Prader-Willi Syndrome Using Epigenome Editing Technology

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Showing item 1 of 3.

This Month in Science

Showing item 1 of 3.

1: Organoid Transplantation Improves Survival in Short Bowel Syndrome Models by Providing Bile Acid Absorption Function / 2: Rethinking the Value of Atrial Fibrillation Screening — What Risks Should Be Targeted?

1: Development of a Method to Restore the Function of Lost Genes in Prader-Willi Syndrome Using Epigenome Editing Technology

1: Elucidating a New Role for "ATRX Aggregates" in Determining Neural Progenitor Cell Fate / 2: Diverse Manifestations of Sjögren's Disease Caused by Differences in Autoantibodies — Elucidating Pathogenesis through Single-Cell and Spatial Analysis —

This Month in Science