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Extracellular small heat shock proteins: exosomal biogenesis and function

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Cell Stress and Chaperones Aims and scope

Abstract

Small heat shock proteins (sHsps) belong to the family of heat shock proteins (Hsps): some are induced in response to multiple stressful events to protect the cells while others are constitutively expressed. Until now, it was believed that Hsps, including sHsps, are present inside the cells and perform intracellular functions. Interestingly, several groups recently reported the extracellular presence of Hsps, and sHsps have also been detected in sera/cerebrospinal fluids in various pathological conditions. Secretion into the extracellular milieu during many pathological conditions suggests additional or novel functions of sHsps in addition to their intracellular properties. Extracellular sHsps are implicated in cell-cell communication, activation of immune cells, and promoting anti-inflammatory and anti-platelet responses. Interestingly, exogenous administration of sHsps showed therapeutic effects in multiple disease models implying that extracellular sHsps are beneficial in pathological conditions. sHsps do not possess signal sequence and, hence, are not exported through the classical Endoplasmic reticulum-Golgi complex (ER-Golgi) secretory pathway. Further, export of sHsps is not inhibited by ER-Golgi secretory pathway inhibitors implying the involvement of a nonclassical secretory pathway in sHsp export. In lieu, lysoendosomal and exosomal pathways have been proposed for the export of sHsps. Heat shock protein 27 (Hsp27), αB-crystallin (αBC), and Hsp20 are shown to be exported by exosomes. Exosomes packaged with sHsps have beneficial effects in in vivo disease models. However, secretion mechanisms and therapeutic use of sHsps have not been elucidated in detail. Therefore, this review aimed at highlighting the current understanding of sHsps (Hsp27, αBC, and Hsp20) in the extracellular medium.

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Acknowledgments

This work is supported by the Science and Engineering Research Board-Early Career Research (SERB-ECR) grant (ECR 2017/000277/LS), Government of India to VSR. MSK is supported by a National Institutes of Health grant (NHLBI 1R01 HL134801) and a USA Department of Defense grant (W81XWH-17-1-0666). JT is supported by Research Initiation Grant (BITS/GAU/RIG/2017/77) and OPERA award (FR/SCM/160317/BIO) from BITS-Pilani, Hyderabad Campus, India. GBR is supported by grants from SERB (SB/S0/HS-192/2013), Department of Biotechnology (BT/PR10658/PFN/20/806/201) and Department of Health Research (DHR/HRD/Fellowship/SUG-04/2015-16), Government of India.

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Authors and Affiliations

  1. Biochemistry Division, National Institute of Nutrition, Tarnaka, Jamai-Osmania, Hyderabad, 500007, India

    V. Sudhakar Reddy & G. Bhanuprakash Reddy

  2. Division of Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Satish K. Madala

  3. Department of Biological Sciences, BITS-Pilani, 500078, Hyderabad Campus, Hyderabad, Telangana, India

    Jamma Trinath

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  1. V. Sudhakar Reddy
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  2. Satish K. Madala
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  3. Jamma Trinath
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  4. G. Bhanuprakash Reddy
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Correspondence to V. Sudhakar Reddy or G. Bhanuprakash Reddy.

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Reddy, V.S., Madala, S.K., Trinath, J. et al. Extracellular small heat shock proteins: exosomal biogenesis and function. Cell Stress and Chaperones 23, 441–454 (2018). https://doi.org/10.1007/s12192-017-0856-z

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  • DOI: https://doi.org/10.1007/s12192-017-0856-z

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