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Gamma secretase activity modulates BMP-7-induced dendritic growth in primary rat sympathetic neurons.
Karunungan, Krystal; Garza, Rachel H; Grodzki, Ana Cristina; Holt, Megan; Lein, Pamela J; Chandrasekaran, Vidya.
Afiliação
  • Karunungan K; Department of Biology, Saint Mary's College of California, 1928 Saint Mary's Road, Moraga, CA 94556, United States of America.
  • Garza RH; Department of Biology, Saint Mary's College of California, 1928 Saint Mary's Road, Moraga, CA 94556, United States of America.
  • Grodzki AC; Department of Molecular Biosciences, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA 95616, United States of America.
  • Holt M; Department of Biology, Saint Mary's College of California, 1928 Saint Mary's Road, Moraga, CA 94556, United States of America.
  • Lein PJ; Department of Molecular Biosciences, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA 95616, United States of America.
  • Chandrasekaran V; Department of Biology, Saint Mary's College of California, 1928 Saint Mary's Road, Moraga, CA 94556, United States of America. Electronic address: vc5@stmarys-ca.edu.
Auton Neurosci ; 247: 103085, 2023 07.
Article em En | MEDLINE | ID: mdl-37031474
Autonomic dysfunction has been observed in Alzheimer's disease (AD); however, the effects of genes involved in AD on the peripheral nervous system are not well understood. Previous studies have shown that presenilin-1 (PSEN1), the catalytic subunit of the gamma secretase (γ-secretase) complex, mutations in which are associated with familial AD function, regulates dendritic growth in hippocampal neurons. In this study, we examined whether the γ-secretase pathway also influences dendritic growth in primary sympathetic neurons. Using immunoblotting and immunocytochemistry, molecules of the γ-secretase complex, PSEN1, PSEN2, PEN2, nicastrin and APH1a, were detected in sympathetic neurons dissociated from embryonic (E20/21) rat sympathetic ganglia. Addition of bone morphogenetic protein-7 (BMP-7), which induces dendrites in these neurons, did not alter expression or localization of γ-secretase complex proteins. BMP-7-induced dendritic growth was inhibited by siRNA knockdown of PSEN1 and by three γ-secretase inhibitors, γ-secretase inhibitor IX (DAPT), LY-411575 and BMS-299897. These effects were specific to dendrites and concentration-dependent and did not alter early downstream pathways of BMP signaling. In summary, our results indicate that γ-secretase activity enhances BMP-7 induced dendritic growth in sympathetic neurons. These findings provide insight into the normal cellular role of the γ-secretase complex in sympathetic neurons.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Secretases da Proteína Precursora do Amiloide / Proteína Morfogenética Óssea 7 Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Secretases da Proteína Precursora do Amiloide / Proteína Morfogenética Óssea 7 Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article