Direct binding of the ligand PSG17 to CD9 requires a CD9 site essential for sperm-egg fusion.

Abstract:

:The function currently attributed to tetraspanins is to organize molecular complexes in the plasma membrane by using multiple cis-interactions. Additionally, the tetraspanin CD9 may be a receptor that binds the soluble ligand PSG17, a member of the immunoglobulin superfamily (IgSF)/CEA subfamily. However, previous data are also consistent with the PSG17 receptor being a CD9 cis-associated protein. In the current study, CD9 extracellular loop (EC2) specifically bound to PSG17-coated beads, indicating a direct interaction between the two proteins. However, CD9-EC2 did not bind to PSG17-coated beads if the CD9-EC2 had the mutation SFQ (173-175) to AAA, a previously studied mutation in egg CD9 that abolishes sperm-egg fusion. Also, PSG17 bound to 293 T cells transfected with wild-type CD9 but not the mutant CD9. By immunofluorescence, PSG17 bound to wild-type eggs but not to CD9 null eggs. The presence of approximately 2 microM recombinant PSG17 produced a significant and reversible inhibition (60-80%) of sperm-egg fusion. Thus, we conclude that CD9 is a receptor for PSG17 and when the PSG17 binding site is mutated or occupied, sperm-egg fusion is impaired. These findings suggest that egg CD9 may function in gamete fusion by binding to a sperm IgSF/CEA subfamily member and such proteins have previously been identified on sperm.

journal_name

Mol Biol Cell

authors

Ellerman DA,Ha C,Primakoff P,Myles DG,Dveksler GS

doi

10.1091/mbc.e03-04-0244

keywords:

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

5098-103

issue

12

eissn

1059-1524

issn

1939-4586

pii

E03-04-0244

journal_volume

14

pub_type

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