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Title: LRSAM1 E3 ubiquitin ligase: molecular neurobiological perspectives linked with brain diseases
Authors: Mishra R.
Upadhyay A.
Prajapati V.K.
Dhiman R.
Poluri, Krishna Mohan
Jana N.R.
Mishra A.
Published in: Cellular and Molecular Life Sciences
Abstract: Cellular protein quality control (PQC) plays a significant role in the maintenance of cellular homeostasis. Failure of PQC mechanism may lead to various neurodegenerative diseases due to accumulation of aberrant proteins. To avoid such fatal neuronal conditions PQC employs autophagy and ubiquitin proteasome system (UPS) to degrade misfolded proteins. Few quality control (QC) E3 ubiquitin ligases interplay an important role to specifically recognize misfolded proteins for their intracellular degradation. Leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1) is a really interesting new gene (RING) class protein that possesses E3 ubiquitin ligase activity with promising applications in PQC. LRSAM1 is also known as RING finger leucine repeat rich (RIFLE) or TSG 101-associated ligase (TAL). LRSAM1 has various cellular functions as it modulates the protein aggregation, endosomal sorting machinery and virus egress from the cells. Thus, this makes LRSAM1 interesting to study not only in protein conformational disorders such as neurodegeneration but also in immunological and other cancerous disorders. Furthermore, LRSAM1 interacts with both cellular protein degradation machineries and hence it can participate in maintenance of overall cellular proteostasis. Still, more research work on the quality control molecular functions of LRSAM1 is needed to comprehend its roles in various protein aggregatory diseases. Earlier findings suggest that in a mouse model of Charcot–Marie–Tooth (CMT) disease, lack of LRSAM1 functions sensitizes peripheral axons to degeneration. It has been observed that in CMT the patients retain dominant and recessive mutations of LRSAM1 gene, which encodes most likely a defective protein. However, still the comprehensive molecular pathomechanism of LRSAM1 in neuronal functions and neurodegenerative diseases is not known. The current article systematically represents the molecular functions, nature and detailed characterization of LRSAM1 E3 ubiquitin ligase. Here, we review emerging molecular mechanisms of LRSAM1 linked with neurobiological functions, with a clear focus on the mechanism of neurodegeneration and also on other diseases. Better understanding of LRSAM1 neurobiological and intracellular functions may contribute to develop promising novel therapeutic approaches, which can also propose new lines of molecular beneficial targets for various neurodegenerative diseases. © 2019, Springer Nature Switzerland AG.
Citation: Cellular and Molecular Life Sciences(2019), 76(11): 2093-2110
Issue Date: 2019
Publisher: Birkhauser Verlag AG
Keywords: Chaperone
Misfolded proteins
ISSN: 1420682X
Author Scopus IDs: 56767511300
Author Affiliations: Mishra, R., Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan 342037, India
Upadhyay, A., Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan 342037, I
Funding Details: Acknowledgements Support for this work was obtained from Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India grant to (AM) EMR/2016/000716.AU received research fellowship in the duration of the work fro
Corresponding Author: Mishra, A.; Cellular and Molecular Neurobiology Unit, Indian Institute of Technology JodhpurIndia; email:
Appears in Collections:Journal Publications [BT]

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