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<p>Solute carrier (SLC) transporters govern most of the chemical exchange across cellular membranes and are integral to metabolic regulation, which in turn is linked to cellular function and identity. Despite their key role, individual functions of the SLC superfamily members were not evaluated systematically. We determined the metabolic and transcriptional profiles upon SLC overexpression in knock-out or wild-type isogenic cell backgrounds for 378 SLCs and 441 SLCs, respectively. Targeted metabolomics provided a fingerprint of 189 intracellular metabolites, while transcriptomics offered insights into cellular programs modulated by SLC expression. Beyond the metabolic profiles of 102 SLCs directly related to their known substrates, we identified putative substrates or metabolic pathway connections for 71 SLCs without previously annotated bona fide substrates, including SLC45A4 as a new polyamine transporter. By comparing the molecular profiles, we identified functionally related SLC groups, including some with distinct impacts on osmolyte balancing and glycosylation. The assessment of functionally related human genes presented here may serve as a blueprint for other systematic studies and supports future investigations into the functional roles of SLCs.</p>

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Metabolic mapping of the human solute carrier superfamily

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月12日

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  • Tabea Wiedmer,
  • Shao Thing Teoh,
  • Eirini Christodoulaki,
  • Gernot Wolf,
  • Chengzhe Tian,
  • Vitaly Sedlyarov,
  • Abigail Jarret,
  • Philipp Leippe,
  • Fabian Frommelt,
  • Alvaro Ingles-Prieto,
  • Sabrina Lindinger,
  • Barbara M G Barbosa,
  • Svenja Onstein,
  • Christoph Klimek,
  • Julio Garcia,
  • Iciar Serrano,
  • Daniela Reil,
  • Diana Santacruz,
  • Mary Piotrowski,
  • Stephen Noell,
  • Christoph Bueschl,
  • Huanyu Li,
  • Gamma Chi,
  • Stefan Mereiter,
  • Tiago Oliveira,
  • Josef M Penninger,
  • David B Sauer,
  • Claire M Steppan,
  • Coralie Viollet,
  • Kristaps Klavins,
  • J Thomas Hannich,
  • Ulrich Goldmann,
  • Giulio Superti-Furga

摘要

Solute carrier (SLC) transporters govern most of the chemical exchange across cellular membranes and are integral to metabolic regulation, which in turn is linked to cellular function and identity. Despite their key role, individual functions of the SLC superfamily members were not evaluated systematically. We determined the metabolic and transcriptional profiles upon SLC overexpression in knock-out or wild-type isogenic cell backgrounds for 378 SLCs and 441 SLCs, respectively. Targeted metabolomics provided a fingerprint of 189 intracellular metabolites, while transcriptomics offered insights into cellular programs modulated by SLC expression. Beyond the metabolic profiles of 102 SLCs directly related to their known substrates, we identified putative substrates or metabolic pathway connections for 71 SLCs without previously annotated bona fide substrates, including SLC45A4 as a new polyamine transporter. By comparing the molecular profiles, we identified functionally related SLC groups, including some with distinct impacts on osmolyte balancing and glycosylation. The assessment of functionally related human genes presented here may serve as a blueprint for other systematic studies and supports future investigations into the functional roles of SLCs.