Involvement of Huntingtin in Development and Ciliary Beating Regulation of Larvae of the Sea Urchin, Hemicentrotus pulcherrimus.

Hideki Katow,Hiromi Yoshida,Masato Kiyomoto,Tomoko Katow

doi:10.3390/ijms22105116

Hideki Katow, Hiromi Yoshida + Show 2 more

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https://doi.org/10.3390/ijms22105116

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Abstract

The multiple functions of the wild type Huntington’s disease protein of the sea urchin Hemicentrotus pulcherrimus (Hp-Htt) have been examined using the anti-Hp-Htt antibody (Ab) raised against synthetic oligopeptides. According to immunoblotting, Hp-Htt was detected as a single band at around the 350 kDa region at the swimming blastula stage to the prism larva stage. From the 2-arm pluteus stage (2aPL), however, an additional smaller band at the 165 kDa region appeared. Immunohistochemically, Hp-Htt was detected in the nuclei and the nearby cytoplasm of the ectodermal cells from the swimming blastula stage, and the blastocoelar cells from the mid-gastrula stage. The Ab-positive signal was converged to the ciliary band-associated strand (CBAS). There, it was accompanied by several CBAS-marker proteins in the cytoplasm, such as glutamate decarboxylase. Application of Hp-Htt morpholino (Hp-Htt-MO) has resulted in shortened larval arms, accompanied by decreased 5-bromo-2-deoxyuridin (BrdU) incorporation by the ectodermal cells of the larval arms. Hp-Htt-MO also resulted in lowered ciliary beating activity, accompanied by a disordered swirling pattern formation around the body. These Hp-Htt-MO-induced deficiencies took place after the onset of CBAS system formation at the larval arms. Thus, Hp-Htt is involved in cell proliferation and the ciliary beating pattern regulation signaling system in pluteus larvae.

Highlights

Accepted: 3 May 2021Huntington’s disease (HD) is a major neurodegenerative disorder in humans, involving involuntary body movements and dementia in the later stages, which is caused by the mutation of a gene, huntingtin (HTT)
OR 97370 USA), and we examined its effects on ciliary band-associated strand (CBAS) formation and ciliary beating
At the 2-arm pluteus stage (2aPL) stage, the Hp-Htt was split into two bands by creating a new smaller

Summary

Introduction

Accepted: 3 May 2021Huntington’s disease (HD) is a major neurodegenerative disorder in humans, involving involuntary body movements and dementia in the later stages, which is caused by the mutation of a gene, huntingtin (HTT). In the mutant Htt, the N-terminal region that contains cytosine-adenine-guanine (CAG) repeats expand extensively and subjected to be numerous neuropathological studies, including its molecular mechanisms [1]. The wild-type Htt, on the other hand, appears to be essential for embryogenesis [2], such as ciliogenesis and neurogenesis in Xenopus [3]. It is involved in intracellular trafficking for extracellular matrix construction [4] and axonal transportation in mammals and a marine snail Aplysia [5]. There seems to be no neurodegenerative disorders in these animals, nor have CAG repeats been found to be involved in the above marine invertebrates to date. Based on an in situ hybridization study, He-HTT and Sp-HTT were found to not be expressed in the neural

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