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The role of transthyretin in cell biology: impact on human pathophysiology

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Abstract

Transthyretin (TTR) is an extracellular protein mainly produced in the liver and choroid plexus, with a well-stablished role in the transport of thyroxin and retinol throughout the body and brain. TTR is prone to aggregation, as both wild-type and mutated forms of the protein can lead to the accumulation of amyloid deposits, resulting in a disease called TTR amyloidosis. Recently, novel activities for TTR in cell biology have emerged, ranging from neuronal health preservation in both central and peripheral nervous systems, to cellular fate determination, regulation of proliferation and metabolism. Here, we review the novel literature regarding TTR new cellular effects. We pinpoint TTR as major player on brain health and nerve biology, activities that might impact on nervous systems pathologies, and assign a new link between TTR and angiogenesis and cancer. We also explore the molecular mechanisms underlying TTR activities at the cellular level, and suggest that these might go beyond its most acknowledged carrier functions and include interaction with receptors and activation of intracellular signaling pathways.

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Funding

The authors were supported by the FEDER – Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT – Fundação Para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01–0145-FEDER-028336 (PTDC/MED-NEU/28336/2017). JE is a FCT fellow (SFRH/BD/116343/2016), JM is a research scientist under the project PTDC/MED-NEU/28336/2017. MAL is a FCT Investigator (IF/00902/2015).

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  1. Joana Magalhães and Márcia Almeida Liz authors contributed equally to this work.

Authors and Affiliations

  1. Neurodegeneration Team, Nerve Regeneration Group, IBMC – Instituto de Biologia Molecular e Celular and i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

    Joana Magalhães, Jessica Eira & Márcia Almeida Liz

  2. ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade Do Porto, Porto, Portugal

    Jessica Eira

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  1. Joana Magalhães
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  2. Jessica Eira
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JM and JE performed the literature search and wrote the manuscript. JM and MAL conceived the structure and content. MAL critically revised the work.

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Correspondence to Márcia Almeida Liz.

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Magalhães, J., Eira, J. & Liz, M.A. The role of transthyretin in cell biology: impact on human pathophysiology. Cell. Mol. Life Sci. 78, 6105–6117 (2021). https://doi.org/10.1007/s00018-021-03899-3

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