BIOLOGY

OF

46, 186-191 (1992)

REPRODUCTION

Mouse

Gamete

Adhesion M. WASSARMAN2

PAUL

Department

of Cell

and Roche

Molecules1

Developmental Biology, Research Center, Nutley,

Roche Institute of Molecular New Jersey 07110

Biology

ABSTRACT Complementary specific after

adhesion

molecules

between

sperm

interactions gamete

fusion

cellular

coat,

sperm

recognize

sperm

undergo

protein

called

assists

or

zona the

sp56,

egg-binding

bind

protein.

sperm

remain

sperm

receptor.

protein.

which

and,

regulate

sperm

(0-)

associated

perhaps,

other

with egg

other

in

linked

binds 000-M,

inner

and

adhesion the

to certain zona

zona

in mice

sperm

0-linked

Thus,

possibly

molecules

(pro

regulate

proteins

Here, I summarize briefly certain aspects of research that have gone on in my laboratory during the past 12 years or so. I focus on the current status of our attempts to identify

characterize those molecules associated with the surface of mouse eggs and sperm that regulate species-specific gamete adhesion before and after fusion of gametes. We have made considerable headway with the egg surface (zona

[12], by plasma membrane Thus, sperm receptors and

pellucida) components stitutes the bulk of the

undergo the tosis required

and, consequently, this aspect presentation. It should be noted

Most viewed

of

the

apply beings.

research

previously

summarized

[1-81.

Much

here

more

drawn other has

inclusive

DEFINITION The nomenclature that used historically mete

adhesion

invertebrate to which surface and

fertilization,

for

component(s) eggs

to which

Thus,

eggs

species-specffic

is attributable

been

re-

9-111 of the

on

with egg respectively.

Health

1985,

(NICHO), ‘Correspondence.

this

research

National FAX:

Science

was

supported

Foundation,

The

in

mouse

and

up

the

we call egg-bind-

sulfides.

by the

Rockefeller

000-M,

primwy as secondary

serves

as secondary

and

Homologous

complementary

sperm

between

sperm

between

National

zona

egg-

Institutes

re-

acrosome-intact sperm bind coat, or zona pellucida

overlying egg-binding

reaction,

order

for

their heads proteins

sperm

(Fig. 1). are asso-

plasma

and sperm of sperm

mem-

to eggs,

sperm

a form of cellular exocyto penetrate the zona

the Mouse

sperm

receptor

Sperm

Receptor

is an 83 000

[4, 15-17]. mZP2 and mZP3 every 140-150 A or so, along

lucida

dimers, ments, identical

formed

and

56

serves

in mice.

pellucida After binding

acrosome

mZP3,

component(s) receptors. The sperm

in part

)acrosin,

sperm

zona

extracellular

coat

in

interconnected held together

turn, are polypeptides The

three

pellucida

(-7

glycoproteins

by noncovalent

are

glycoprotein

Mr

glycoproteins,

account egg

present

as heterothat make

the filaments

.tm

thick)

for virzona pcI-

[4, 18].

of

threonine

Foundation.

significantly

201.235-2839.

186

residues,

similar

of 402 amino is particularly

The

fila-

by mZP1, a dimer by intermolecular are

held

together

of di-

in the

bonds.

While mZP3 has a heterogeneous appearance quent to gel electrophoresis, it possesses a unique peptide consisting The polypeptide

‘Through

A

[14].

and field

vertebrate

adhesion

to complexes

egg.

eggs.

polyspermy

surface bind,

since to mZP3,

that we call mZP3 [7]. mZP3 and two other mZPI (200 000 Mr) and mZP2 (120 000 Mr), tually all of the mass (3-4 ng) of the mouse

both

extra-

pellucida and fuse with egg plasma membrane [13]. Following fusion of gametes, fertilized eggs undergo the cortical reaction, a form of cellular exocytosis required for establishment of the zona reaction and “slow” block to

from mam-

adopted is in keeping with molecules that support ga-

animal systems. The egg sperm bind, we call sperm

ing proteins.

conthat

OF TERMS

we have to describe

during

ciated brane,

discussions

of mammalian fertilization are available [e.g., should be consulted for a broader perspective than that presented here.

shortly egg

Acrosome-reacted

In mice, motile, capacitated, to the ovulated egg extracellular

and

our research on mice mals, including human

species-

is a putative

mZP2

fertilization

on

that conclusions as well to many

the

heads,

oligosaccharides.

glycoprotein.

membrane,

in the of binding

fertilize

and

mouse

mZP3

located

As a consequence

ceptors

to suggest

molecules

is carbohydrate-mediated,

binding

is evidence

support

of these

mammals.

INTRODUCTION

there

molecules

glycoprotein

pellucida

pellucida

surface

These

Modification

acrosome-intact

acrosomal

sperm

sperm.

oiigosaccharides.

to penetrate

and

and

an 83 000-M,

Gamete

surrounding a 120

mZP2,

protease fertilization

them

eggs

(fertilization).

mZP3,

receptor.

recognizes

with

fusion

fertilization.

membrane

sp56

of mouse

surfuce

to gamete

enables

in plasma that

a sperm

lead

the

serine/threonine-

by interacting

These

apparently

molecules

reaction,

It is suggested

Perhaps

that

as primary

mZP3

is located

to eggs

bound

egg-binding

serves

acrosome

on

of polyspermic

to certain

which

located

eggs

and

in prevention

pellucida,

and

are

acids rich

(44 000 in proline,

Mr)

subse-

poly-

[15, 19,201. serine, and

possesses very little a-helix, and is not to any other entries in protein data bases.

GAMETE

FIG. 1. micrograph

The

heterogeneous

its asparagine-

appearance (N-) linked and

oligosaccharides. type, N-linked ber of 0-linked charides also 4.7)

of mZP3. The mZP3

(chromosome tion unit, -8.6

Light micrograph was taken using

mZP3

glycoprotein

three

or

four

by a single-copy

sequences

in 5’ flanking

region

relatively

470 bp) to the transcriptional start-site Lira, S.A., Wassarman, P.M., unpublished]. cumulates to extremely high steady-state cyte growth (-300 000 copies/oocyte)

tectable

levels

(