Importance of Reelin C-terminal region in the development and maintenance of the postnatal cerebral cortex and its regulation by specific proteolysis

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Takao KohnoMitsuharu Hattori

Abstract

During brain development, Reelin exerts a variety of effects in a context-dependent manner, whereas its underlying molecular mechanisms remain poorly understood. We previously showed that the C-terminal region (CTR) of Reelin is required for efficient induction of phosphorylation of Dab1, an essential adaptor protein for canonical Reelin signaling. However, the physiological significance of the Reelin CTR in vivo remains unexplored. To dissect out Reelin functions, we made a knock-in (KI) mouse in which the Reelin CTR is deleted. The amount of Dab1, an indication of canonical Reelin signaling strength, is increased in the KI mouse, indicating that the CTR is necessary for efficient induction of Dab1 phosphorylation in vivo. Formation of layer structures during embryonic development is normal in the KI mouse. Intriguingly, the marginal zone (MZ) of the cerebral cortex becomes narrower at postnatal stages because upper-layer neurons invade the MZ and their apical dendrites are misoriented and poorly branched. Furthermore, Reelin undergoes proteolytic cleavage by proprotein convertases at a site located 6 residues from the C terminus, and it was suggested that this cleavage abrogates the Reelin binding to the neuronal cell membran...Continue Reading

Citations

Apr 12, 2016·Frontiers in Cellular Neuroscience·April L LussierG William Rebeck
Apr 2, 2016·Neuroscience Research·Tomoharu MizukamiMitsuharu Hattori
Jun 1, 2016·Frontiers in Cellular Neuroscience·Gum Hwa Lee, Gabriella D'Arcangelo
Jun 16, 2016·Frontiers in Cellular Neuroscience·Fanomezana M RanaivosonDavide Comoletti
Nov 3, 2016·Frontiers in Cellular Neuroscience·Kazuhiro IshiiKazunori Nakajima
Mar 16, 2017·Journal of Lipid Research·Courtney Lane-Donovan, Joachim Herz
Mar 30, 2018·The Journal of Biological Chemistry·Sarah L KingHans H Wandall
Oct 3, 2017·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Takao Kohno
Dec 4, 2019·Psychiatry and Clinical Neurosciences·Ken-Ichiro Kubo
Jul 26, 2016·Frontiers in Cellular Neuroscience·Hans H Bock, Petra May
Feb 23, 2020·Frontiers in Pharmacology·Qingqing XuShunying Yu
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Mar 5, 2019·Biological & Pharmaceutical Bulletin·Yuko YamakageMitsuharu Hattori
Feb 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Yuki MatsunagaKazunori Nakajima
Oct 15, 2019·Frontiers in Behavioral Neuroscience·Elisa Dalla VecchiaWilliam H J Norton
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Yumiko Hatanaka, Tatsumi Hirata
Feb 11, 2021·Journal of Biochemistry·Mitsuharu Hattori, Takao Kohno
Aug 28, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Masahito SawahataKiyofumi Yamada
Aug 21, 2021·Development·Mohammad I K HamadEckart Förster

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