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The ion channel TRPV5 regulates B-cell signaling and activation.
Mahtani, Trisha; Sheth, Hena; Smith, L K; Benedict, Leshawn; Brecier, Aurelie; Ghasemlou, Nader; Treanor, Bebhinn.
Afiliación
  • Mahtani T; Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.
  • Sheth H; Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.
  • Smith LK; Department of Biological Sciences, University of Toronto Scarborough, Toronto, ON, Canada.
  • Benedict L; Department of Biological Sciences, University of Toronto Scarborough, Toronto, ON, Canada.
  • Brecier A; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
  • Ghasemlou N; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
  • Treanor B; Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.
Front Immunol ; 15: 1386719, 2024.
Article en En | MEDLINE | ID: mdl-38694510
ABSTRACT

Introduction:

B-cell activation triggers the release of endoplasmic reticulum calcium stores through the store-operated calcium entry (SOCE) pathway resulting in calcium influx by calcium release-activated calcium (CRAC) channels on the plasma membrane. B-cell-specific murine knockouts of SOCE do not impact humoral immunity suggesting that alternative channels may be important.

Methods:

We identified a member of the calcium-permeable transient receptor potential (TRP) ion channel family, TRPV5, as a candidate channel expressed in B cells by a quantitative polymerase chain reaction (qPCR) screen. To further investigate the role of TRPV5 in B-cell responses, we generated a murine TRPV5 knockout (KO) by CRISPR-Cas9.

Results:

We found TRPV5 polarized to B-cell receptor (BCR) clusters upon stimulation in a PI3K-RhoA-dependent manner. TRPV5 KO mice have normal B-cell development and mature B-cell numbers. Surprisingly, calcium influx upon BCR stimulation in primary TRPV5 KO B cells was not impaired; however, differential expression of other calcium-regulating proteins, such as ORAI1, may contribute to a compensatory mechanism for calcium signaling in these cells. We demonstrate that TRPV5 KO B cells have impaired spreading and contraction in response to membrane-bound antigen. Consistent with this, TRPV5 KO B cells have reduced BCR signaling measured through phospho-tyrosine residues. Lastly, we also found that TRPV5 is important for early T-dependent antigen specific responses post-immunization.

Discussion:

Thus, our findings identify a role for TRPV5 in BCR signaling and B-cell activation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Activación de Linfocitos / Receptores de Antígenos de Linfocitos B / Ratones Noqueados / Señalización del Calcio / Canales Catiónicos TRPV Límite: Animals Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Activación de Linfocitos / Receptores de Antígenos de Linfocitos B / Ratones Noqueados / Señalización del Calcio / Canales Catiónicos TRPV Límite: Animals Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza