Lipophorin receptors regulate mushroom body development and complex behaviors in Drosophila.
Animals
Cell Adhesion Molecules, Neuronal
/ genetics
Drosophila Proteins
/ genetics
Drosophila melanogaster
/ genetics
Extracellular Matrix Proteins
/ genetics
Mushroom Bodies
/ metabolism
Nerve Tissue Proteins
/ genetics
Receptors, Cytoplasmic and Nuclear
/ metabolism
Reelin Protein
Serine Endopeptidases
/ metabolism
Dab
Lipophorin receptor
Lipoprotein receptor
Mushroom bodies
Neurite morphogenesis
Neuronal development
Reelin
Journal
BMC biology
ISSN: 1741-7007
Titre abrégé: BMC Biol
Pays: England
ID NLM: 101190720
Informations de publication
Date de publication:
07 09 2022
07 09 2022
Historique:
received:
07
12
2021
accepted:
17
08
2022
entrez:
7
9
2022
pubmed:
8
9
2022
medline:
11
9
2022
Statut:
epublish
Résumé
Drosophila melanogaster lipophorin receptors (LpRs), LpR1 and LpR2, are members of the LDLR family known to mediate lipid uptake in a range of organisms from Drosophila to humans. The vertebrate orthologs of LpRs, ApoER2 and VLDL-R, function as receptors of a glycoprotein involved in development of the central nervous system, Reelin, which is not present in flies. ApoER2 and VLDL-R are associated with the development and function of the hippocampus and cerebral cortex, important association areas in the mammalian brain, as well as with neurodevelopmental and neurodegenerative disorders linked to those regions. It is currently unknown whether LpRs play similar roles in the Drosophila brain. We report that LpR-deficient flies exhibit impaired olfactory memory and sleep patterns, which seem to reflect anatomical defects found in a critical brain association area, the mushroom bodies (MB). Moreover, cultured MB neurons respond to mammalian Reelin by increasing the complexity of their neurite arborization. This effect depends on LpRs and Dab, the Drosophila ortholog of the Reelin signaling adaptor protein Dab1. In vitro, two of the long isoforms of LpRs allow the internalization of Reelin, suggesting that Drosophila LpRs interact with human Reelin to induce downstream cellular events. These findings demonstrate that LpRs contribute to MB development and function, supporting the existence of a LpR-dependent signaling in Drosophila, and advance our understanding of the molecular factors functioning in neural systems to generate complex behaviors in this model. Our results further emphasize the importance of Drosophila as a model to investigate the alterations in specific genes contributing to neural disorders.
Sections du résumé
BACKGROUND
Drosophila melanogaster lipophorin receptors (LpRs), LpR1 and LpR2, are members of the LDLR family known to mediate lipid uptake in a range of organisms from Drosophila to humans. The vertebrate orthologs of LpRs, ApoER2 and VLDL-R, function as receptors of a glycoprotein involved in development of the central nervous system, Reelin, which is not present in flies. ApoER2 and VLDL-R are associated with the development and function of the hippocampus and cerebral cortex, important association areas in the mammalian brain, as well as with neurodevelopmental and neurodegenerative disorders linked to those regions. It is currently unknown whether LpRs play similar roles in the Drosophila brain.
RESULTS
We report that LpR-deficient flies exhibit impaired olfactory memory and sleep patterns, which seem to reflect anatomical defects found in a critical brain association area, the mushroom bodies (MB). Moreover, cultured MB neurons respond to mammalian Reelin by increasing the complexity of their neurite arborization. This effect depends on LpRs and Dab, the Drosophila ortholog of the Reelin signaling adaptor protein Dab1. In vitro, two of the long isoforms of LpRs allow the internalization of Reelin, suggesting that Drosophila LpRs interact with human Reelin to induce downstream cellular events.
CONCLUSIONS
These findings demonstrate that LpRs contribute to MB development and function, supporting the existence of a LpR-dependent signaling in Drosophila, and advance our understanding of the molecular factors functioning in neural systems to generate complex behaviors in this model. Our results further emphasize the importance of Drosophila as a model to investigate the alterations in specific genes contributing to neural disorders.
Identifiants
pubmed: 36071487
doi: 10.1186/s12915-022-01393-1
pii: 10.1186/s12915-022-01393-1
pmc: PMC9454125
doi:
Substances chimiques
Cell Adhesion Molecules, Neuronal
0
Drosophila Proteins
0
Extracellular Matrix Proteins
0
Lpr1 protein, Drosophila
0
Nerve Tissue Proteins
0
Receptors, Cytoplasmic and Nuclear
0
Reelin Protein
0
dab protein, Drosophila
0
lipophorin receptor
0
Serine Endopeptidases
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
198Informations de copyright
© 2022. The Author(s).
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