Compartmentalization of a unique ADP/ATP carrier protein SFEC (Sperm Flagellar Energy Carrier, AAC4) with glycolytic enzymes in the fibrous sheath of the human sperm flagellar principal piece.
The longest part of the sperm flagellum, the principal piece, contains the fibrous sheath, a cytoskeletal element unique to spermiogenesis. We performed mass spectrometry proteomics on isolated human fibrous sheaths identifying a unique ADP/ATP carrier protein, SFEC [AAC4], seven glycolytic enzymes previously unreported in the human sperm fibrous sheath, and sorbitol dehydrogenase. SFEC, pyruvate kinase and aldolase were co-localized by immunofluorescence to the principal piece. A homology model constructed for SFEC predicted unique residues at the entrance to the nucleotide binding pocket of SFEC that are absent in other human ADP/ATP carriers, suggesting opportunities for selective drug targeting. This study provides the first evidence of a role for an ADP/ATP carrier family member in glycolysis. The co-localization of SFEC and glycolytic enzymes in the fibrous sheath supports a growing literature that the principal piece of the flagellum is capable of generating and regulating ATP independently from mitochondrial oxidation in the mid-piece. A model is proposed that the fibrous sheath represents a highly ordered complex, analogous to the electron transport chain, in which adjacent enzymes in the glycolytic pathway are assembled to permit efficient flux of energy substrates and products with SFEC serving to mediate energy generating and energy consuming processes in the distal flagellum, possibly as a nucleotide shuttle between flagellar glycolysis, protein phosphorylation and mechanisms of motility.
Kim
Young-Hwan
YH
Center for Research in Contraceptive and Reproductive Health, Department of Cell Biology, University of Virginia, Charlottesville, PO Box 800732, VA 22908, USA.
Haidl
Gerhard
G
Schaefer
Martina
M
Egner
Ursula
U
Mandal
Arabinda
A
Herr
John C
JC
D000595:Amino Acid Sequence; D001483:Base Sequence; D002451:Cell Compartmentation; D006019:Glycolysis; D006801:Humans; D008297:Male; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D040901:Proteomics; D013081:Sperm Motility; D013082:Sperm Tail / Q000201:enzymology / Q000378:metabolism; D013094:Spermatozoa / Q000201:enzymology* / Q000378:metabolism
C518774:SLC25A31 protein, human; D000226:Mitochondrial ADP, ATP Translocases