The molecular identity of the TLQP-21 peptide receptor

Bhavani S. Sahu; Megin E. Nguyen; Pedro Rodriguez; Jean Pierre Pallais; Vinayak Ghosh; Maria Razzoli; Yuk Y. Sham; Stephen R. Salton; Alessandro Bartolomucci

doi:10.1007/s00018-021-03944-1

The molecular identity of the TLQP-21 peptide receptor

Bhavani S. Sahu, Megin E. Nguyen, Pedro Rodriguez, Jean Pierre Pallais, Vinayak Ghosh, Maria Razzoli, Yuk Y. Sham, Stephen R. Salton, Alessandro Bartolomucci

Research output: Contribution to journal › Review article › peer-review

5 Scopus citations

Abstract

The TLQP-21 neuropeptide has been implicated in functions as diverse as lipolysis, neurodegeneration and metabolism, thus suggesting an important role in several human diseases. Three binding targets have been proposed for TLQP-21: C3aR1, gC1qR and HSPA8. The aim of this review is to critically evaluate the molecular identity of the TLQP-21 receptor and the proposed multi-receptor mechanism of action. Several studies confirm a critical role for C3aR1 in TLQP-21 biological activity and a largely conserved mode of binding, receptor activation and signaling with C3a, its first-identified endogenous ligand. Conversely, data supporting a role of gC1qR and HSPA8 in TLQP-21 activity remain limited, with no signal transduction pathways being described. Overall, C3aR1 is the only receptor for which a necessary and sufficient role in TLQP-21 activity has been confirmed thus far. This conclusion calls into question the validity of a multi-receptor mechanism of action for TLQP-21 and should inform future studies.

Original language	English (US)
Pages (from-to)	7133-7144
Number of pages	12
Journal	Cellular and Molecular Life Sciences
Volume	78
Issue number	23
DOIs	https://doi.org/10.1007/s00018-021-03944-1
State	Published - Oct 9 2021

Bibliographical note

Funding Information:
Supported by DK117504 (AB, SRS), DK118150 (AB), DK102496 (AB), AG062355 (SRS), AG062661 (SRS), Cure Alzheimer’s Fund (SRS), University of Minnesota Informatics Institute graduate assistantship program (MEN), T32DK083250 (JPP), BT-/RLF/Re-entry/38/2016, Department of Biotechnology, Government of India, NBRC core funds (BSS).

Funding Information:
We would like to acknowledge current and past members of the Bartolomucci and Salton Labs and several colleagues and collaborator for their significant contribution to the research described in this review. We would also like to acknowledge the BSS lab members for valuable feedback on the manuscript.

Publisher Copyright:
© 2021, The Author(s).

Keywords

Adipocytes
C3a
C3aR1
Complement
G-protein-coupled receptor
gC1QR
HSPA8
Microglia
TLQP-21
VGF

PubMed: MeSH publication types

Journal Article
Review

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00018-021-03944-1

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title = "The molecular identity of the TLQP-21 peptide receptor",

abstract = "The TLQP-21 neuropeptide has been implicated in functions as diverse as lipolysis, neurodegeneration and metabolism, thus suggesting an important role in several human diseases. Three binding targets have been proposed for TLQP-21: C3aR1, gC1qR and HSPA8. The aim of this review is to critically evaluate the molecular identity of the TLQP-21 receptor and the proposed multi-receptor mechanism of action. Several studies confirm a critical role for C3aR1 in TLQP-21 biological activity and a largely conserved mode of binding, receptor activation and signaling with C3a, its first-identified endogenous ligand. Conversely, data supporting a role of gC1qR and HSPA8 in TLQP-21 activity remain limited, with no signal transduction pathways being described. Overall, C3aR1 is the only receptor for which a necessary and sufficient role in TLQP-21 activity has been confirmed thus far. This conclusion calls into question the validity of a multi-receptor mechanism of action for TLQP-21 and should inform future studies.",

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author = "Sahu, \{Bhavani S.\} and Nguyen, \{Megin E.\} and Pedro Rodriguez and Pallais, \{Jean Pierre\} and Vinayak Ghosh and Maria Razzoli and Sham, \{Yuk Y.\} and Salton, \{Stephen R.\} and Alessandro Bartolomucci",

note = "Funding Information: Supported by DK117504 (AB, SRS), DK118150 (AB), DK102496 (AB), AG062355 (SRS), AG062661 (SRS), Cure Alzheimer{\textquoteright}s Fund (SRS), University of Minnesota Informatics Institute graduate assistantship program (MEN), T32DK083250 (JPP), BT-/RLF/Re-entry/38/2016, Department of Biotechnology, Government of India, NBRC core funds (BSS). Funding Information: We would like to acknowledge current and past members of the Bartolomucci and Salton Labs and several colleagues and collaborator for their significant contribution to the research described in this review. We would also like to acknowledge the BSS lab members for valuable feedback on the manuscript. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1007/s00018-021-03944-1",

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T1 - The molecular identity of the TLQP-21 peptide receptor

AU - Sahu, Bhavani S.

AU - Nguyen, Megin E.

AU - Rodriguez, Pedro

AU - Pallais, Jean Pierre

AU - Ghosh, Vinayak

AU - Razzoli, Maria

AU - Sham, Yuk Y.

AU - Salton, Stephen R.

AU - Bartolomucci, Alessandro

N1 - Funding Information: Supported by DK117504 (AB, SRS), DK118150 (AB), DK102496 (AB), AG062355 (SRS), AG062661 (SRS), Cure Alzheimer’s Fund (SRS), University of Minnesota Informatics Institute graduate assistantship program (MEN), T32DK083250 (JPP), BT-/RLF/Re-entry/38/2016, Department of Biotechnology, Government of India, NBRC core funds (BSS). Funding Information: We would like to acknowledge current and past members of the Bartolomucci and Salton Labs and several colleagues and collaborator for their significant contribution to the research described in this review. We would also like to acknowledge the BSS lab members for valuable feedback on the manuscript. Publisher Copyright: © 2021, The Author(s).

PY - 2021/10/9

Y1 - 2021/10/9

N2 - The TLQP-21 neuropeptide has been implicated in functions as diverse as lipolysis, neurodegeneration and metabolism, thus suggesting an important role in several human diseases. Three binding targets have been proposed for TLQP-21: C3aR1, gC1qR and HSPA8. The aim of this review is to critically evaluate the molecular identity of the TLQP-21 receptor and the proposed multi-receptor mechanism of action. Several studies confirm a critical role for C3aR1 in TLQP-21 biological activity and a largely conserved mode of binding, receptor activation and signaling with C3a, its first-identified endogenous ligand. Conversely, data supporting a role of gC1qR and HSPA8 in TLQP-21 activity remain limited, with no signal transduction pathways being described. Overall, C3aR1 is the only receptor for which a necessary and sufficient role in TLQP-21 activity has been confirmed thus far. This conclusion calls into question the validity of a multi-receptor mechanism of action for TLQP-21 and should inform future studies.

AB - The TLQP-21 neuropeptide has been implicated in functions as diverse as lipolysis, neurodegeneration and metabolism, thus suggesting an important role in several human diseases. Three binding targets have been proposed for TLQP-21: C3aR1, gC1qR and HSPA8. The aim of this review is to critically evaluate the molecular identity of the TLQP-21 receptor and the proposed multi-receptor mechanism of action. Several studies confirm a critical role for C3aR1 in TLQP-21 biological activity and a largely conserved mode of binding, receptor activation and signaling with C3a, its first-identified endogenous ligand. Conversely, data supporting a role of gC1qR and HSPA8 in TLQP-21 activity remain limited, with no signal transduction pathways being described. Overall, C3aR1 is the only receptor for which a necessary and sufficient role in TLQP-21 activity has been confirmed thus far. This conclusion calls into question the validity of a multi-receptor mechanism of action for TLQP-21 and should inform future studies.

KW - Adipocytes

KW - C3a

KW - C3aR1

KW - Complement

KW - G-protein-coupled receptor

KW - gC1QR

KW - HSPA8

KW - Microglia

KW - TLQP-21

KW - VGF

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U2 - 10.1007/s00018-021-03944-1

DO - 10.1007/s00018-021-03944-1

M3 - Review article

C2 - 34626205

AN - SCOPUS:85116765239

SN - 1420-682X

VL - 78

SP - 7133

EP - 7144

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

IS - 23

ER -

The molecular identity of the TLQP-21 peptide receptor

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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