The C5 Variant of the Butyrylcholinesterase Tetramer Includes a Noncovalently Bound 60 kDa Lamellipodin Fragment

Lawrence M Schopfer , Hervé Delacour (1) , Patrick Masson , Jacqueline Leroy (2) , Eric Krejci (2) , Oksana Lockridge

1 Hôpital d'Instruction des Armées Begin
2 COGNAC-G - UMR 8257 - Cognition and Action Group

Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30-200% higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel electrophoresis. This band is about 60 kDa larger than wild-type BChE. Umbilical cord BChE in 100% of newborn babies has a C5-like band. Our goal was to identify the unknown, 60 kDa protein in C5. Both wild-type and C5 BChE are under the genetic control of two independent loci, the BCHE gene on Chr 3q26.1 and the RAPH1 (lamellipodin) gene on Chr 2q33. Wild-type BChE tetramers are assembled around a 3 kDa polyproline peptide from lamellipodin. Western blot of boiled C5 and cord BChE showed a positive response with an antibody to the C-terminus of lamellipodin. The C-terminal exon of lamellipodin is about 60 kDa including an N-terminal polyproline. We propose that the unknown protein in C5 and cord BChE is encoded by the last exon of the RAPH1 gene. In 90% of the population, the 60 kDa fragment is shortened to 3 kDa during maturation to adulthood, leaving only 10% of adults with C5 BChE.

Keywords: lamellipodin; RAPH1; butyrylcholinesterase; tetramer; C5 phenotype

Domains: Life Sciences [q-bio]

Lawrence M Schopfer, Hervé Delacour, Patrick Masson, Jacqueline Leroy, Eric Krejci, et al.. The C5 Variant of the Butyrylcholinesterase Tetramer Includes a Noncovalently Bound 60 kDa Lamellipodin Fragment. Molecules, 2017, 22 (7), pp.1083. ⟨10.3390/molecules22071083⟩. ⟨hal-03025653⟩