Leucine/glutamine and v-ATPase/lysosomal acidification via mTORC1 activation are required for position-dependent regeneration

Scientific Reports
Kazuya TakayamaYutaka Kikuchi

Abstract

In animal regeneration, control of position-dependent cell proliferation is crucial for the complete restoration of patterned appendages in terms of both, shape and size. However, detailed mechanisms of this process are largely unknown. In this study, we identified leucine/glutamine and v-ATPase/lysosomal acidification, via mechanistic target of rapamycin complex 1 (mTORC1) activation, as effectors of amputation plane-dependent zebrafish caudal fin regeneration. mTORC1 activation, which functions in cell proliferation, was regulated by lysosomal acidification possibly via v-ATPase activity at 3 h post amputation (hpa). Inhibition of lysosomal acidification resulted in reduced growth factor-related gene expression and suppression of blastema formation at 24 and 48 hpa, respectively. Along the proximal-distal axis, position-dependent lysosomal acidification and mTORC1 activation were observed from 3 hpa. We also report that Slc7a5 (L-type amino acid transporter), whose gene expression is position-dependent, is necessary for mTORC1 activation upstream of lysosomal acidification during fin regeneration. Furthermore, treatment with leucine and glutamine, for both proximal and distal fin stumps, led to an up-regulation in cell prolif...Continue Reading

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Citations

Nov 15, 2019·Wiley Interdisciplinary Reviews. Developmental Biology·Ivonne M Sehring, Gilbert Weidinger
Apr 24, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Matthew P HarrisJennifer Lanni
Oct 23, 2019·Frontiers in Endocrinology·Johannes R SchmidtFranziska Knopf
Feb 11, 2020·Chemical Science·Xiujuan ShiBen Zhong Tang
Sep 4, 2021·Bioelectricity·Pranjal SrivastavaMichael Levin

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Methods Mentioned

BETA
environmental stresses
amputation
PCR
GTPase
amputations

Software Mentioned

ImageJ
FluoView

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