A network map of GDNF/RET signaling pathway in physiological and pathological conditions

Praseeda Mol; Rex Devasahayam Arokia Balaya; Shobha Dagamajalu; Sreeranjini Babu; Pavithra Chandrasekaran; Reshma Raghavan; Sneha Suresh; Namitha Ravishankara; Anu Hemalatha Raju; Bipin Nair; Prashant Kumar Modi; Anita Mahadevan; Thottethodi Subrahmanya Keshava Prasad; Rajesh Raju

doi:10.1007/s12079-023-00726-1

A network map of GDNF/RET signaling pathway in physiological and pathological conditions

J Cell Commun Signal. 2023 Sep;17(3):1089-1095. doi: 10.1007/s12079-023-00726-1. Epub 2023 Jan 30.

Authors

Praseeda Mol^{1

2}, Rex Devasahayam Arokia Balaya³, Shobha Dagamajalu⁴, Sreeranjini Babu⁵, Pavithra Chandrasekaran¹, Reshma Raghavan¹, Sneha Suresh¹, Namitha Ravishankara¹, Anu Hemalatha Raju¹, Bipin Nair², Prashant Kumar Modi⁵, Anita Mahadevan^{6

7}, Thottethodi Subrahmanya Keshava Prasad⁸, Rajesh Raju^{9

10}

Affiliations

¹ Institute of Bioinformatics, International Technology Park, Whitefield, Bangalore, 560066, India.
² Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, 690525, India.
³ Centre for Integrative Omics Data Science, Yenepoya (Deemed to Be University), Mangalore, 575018, India. rexprem@yenepoya.edu.in.
⁴ Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Mangalore, 575018, India. shobha_d@yenepoya.edu.in.
⁵ Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Mangalore, 575018, India.
⁶ Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India.
⁷ Human Brain Tissue Repository, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India.
⁸ Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Mangalore, 575018, India. keshav@yenepoya.edu.in.
⁹ Centre for Integrative Omics Data Science, Yenepoya (Deemed to Be University), Mangalore, 575018, India. rajeshraju@yenepoya.edu.in.
¹⁰ Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Mangalore, 575018, India. rajeshraju@yenepoya.edu.in.

Abstract

Glial cell line-derived neurotrophic factor (GDNF) signals through a multi-component receptor system predominantly consisting of glycosyl-phosphatidylinositol-anchored GDNF family receptor alpha-1 (GFRα1) and the Rearranged during transfection (RET) receptor tyrosine kinase. GDNF/RET signaling is vital to the central and peripheral nervous system, kidney morphogenesis, and spermatogenesis. In addition, the dysregulation of the GDNF/RET signaling has been implicated in the pathogenesis of cancers. Despite the extensive research on GDNF/RET signaling, a molecular network of reactions induced by GDNF reported across the published literature. However, a comprehensive GDNF/RET pathway resource is currently unavailable. We describe an integrated signaling pathway reaction map of GDNF/RET consisting of 1151 molecular reactions. These include information pertaining to 52 molecular association events, 70 enzyme catalysis events, 36 activation/inhibition events, 22 translocation events, 856 gene regulation events, and 115 protein-level expression events induced by GDNF in diverse cell types. We developed a comprehensive GDNF/RET signaling network map based on these molecular reactions. The pathway map was made accessible through WikiPathways database ( https://www.wikipathways.org/index.php/Pathway:WP5143 ). Biocuration and development of gene regulatory network map of GDNF/RET signaling pathway.

Keywords: Multi-component receptor system; Post-translational modifications; Protein–protein interactions; Receptor tyrosine kinases; Signaling network.