The ancient CgPEPCK-1, not CgPECK-2, evolved into a multifunctional molecule as an intracellular enzyme and extracellular PRR.

Dev Comp Immunol

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China.

Published: August 2023

AI Article Synopsis

  • Phosphoenolpyruvate carboxykinase (PEPCK) is crucial for gluconeogenesis, and this study explores its evolutionary differences, particularly in Mollusca with two distinct lineages: Mollusca_PEPCK-1 and Mollusca_PEPCK-2.
  • CgPEPCK-1 and CgPEPCK-2 from the Pacific oyster Crassostrea gigas shared structural similarities but showed different expression levels and functions; CgPEPCK-2 had higher activity, while CgPEPCK-1 was linked to immune responses against infections.
  • The findings suggest that the PEPCK gene family has evolved in Mollusks to specialize, with CgPE

Article Abstract

Phosphoenolpyruvate carboxykinase (PEPCK) is a well-known lyase involved in gluconeogenesis, while their evolution and function differentiation have not been fully understood. In this study, by constructing a phylogenetic tree to examine PEPCKs throughout the evolution from poriferans to vertebrates, Mollusk was highlighted as the only phylum to exhibit two distinct lineages, Mollusca_PEPCK-1 and Mollusca_PEPCK-2. Further study of two representative members from Crassostrea gigas (CgPEPCK-1 and CgPEPCK-2) showed that they both shared conserved sequences and structural characteristics of the catalytic enzyme, while CgPEPCK-2 displayed a higher expression level than CgPEPCK-1 in all tested tissues, and CgPEPCK-1 was specifically implicated in the immune defense against LPS stimulation and Vibrio splendidus infection. Functional analysis revealed that CgPEPCK-2 had stronger enzymatic activity than CgPEPCK-1, while CgPEPCK-1 exhibited stronger binding activity with various PAMPs, and only the protein of CgPEPCK-1 increased significantly in hemolymph during immune stimulation. All results supported that distinct sequence and function differentiations of the PEPCK gene family should have occurred since Mollusk. The more advanced evolutionary branch Mollusca_PEPCK-2 should preserve its essential function as a catalytic enzyme to be more specialized and efficient, while the ancient branch Mollusca_PEPCK-1 probably contained some members, such as CgPEPCK-1, that should be integrated into the immune system as an extracellular immune recognition receptor.

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http://dx.doi.org/10.1016/j.dci.2023.104722DOI Listing

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