Acrogranin, an acrosomal cysteine‐rich glycoprotein, is the precursor of the growth‐modulating peptides, granulins, and epithelins, and is expressed in somatic as well as male germ cells

Abstract

Spermatogenesis is a unique system of differentiation involving cellular remodeling and the biogenesis of sperm-specific organelles. To study the biogenesis of one such organelle, the acrosome, we have been examining the gene expression, biosynthesis, and targeting of specific acrosomal proteins during mammalian spermatogenesis. An acrosomal marker that we recently purified and began characterizing is acrogranin, a 67,000-molecular-weight glycoprotein originally isolated from guinea pig testes. This glycoprotein is detected in pachytene spermatocytes and is found later in the acrosomes of developing spermatids and sperm. Immunoblotting of several tissues and immunofluorescent localization in frozen sections of guinea pig testes suggested that acrogranin was a germ cell-specific glycoprotein that was expressed meiotically and post-meiotically. However, Northern blot analysis demonstrated that the mRNA for acrogranin was ubiquitously expressed in all guinea pig and mouse tissues examined. Furthermore, the primary structures of guinea pig and mouse acrogranins, deduced from the cDNA sequences, reveal that this glycoprotein is a cysteine-rich molecule with a motif that is tandemly repeated seven times, very similar to that of the human epithelin/granulin precursor. We conclude that guinea pig and mouse acrogranins are homologues of the precursor of the human and rat epithelin/granulin peptides previously demonstrated to have growth-modulating properties.

A Novel Hematopoietic Granulin Induces Proliferation of Goldfish (Carassius auratus L.) Macrophages

“…Granulins were first purified from the extracts of human inflammatory cell exudates, and from rat bone marrow (1). To date, seven granulin peptides (A to G) have been characterized (9,10,26,27), and it has been shown that they are generated following proteolytic cleavage of progranulin (7). The two main differences between goldfish granulin and mammalian progranulin were: (a) the goldfish granulin gene encoded for a much smaller protein (159 amino acids); and (b) unlike mammalian progranulin, which has been shown to be expressed ubiquitously in different tissues, the goldfish granulin expression was limited to hematopoietic tissues (kidney and spleen) and blood mononuclear cells.…”

“…The larger precursor is known by several names, including granulin/epithelin precursor (8), proepithelin (9), acrogranin (10), PC cell-derived growth factor (PCDGF) (11), and progranulin. Granulins have a unique 12-cysteine motif that is arranged in four ␤-hairpins, stacked one upon another in a helical formation and connected via a central rod of disulfide bonds (12)(13)(14).…”

“…Structurally, granulins are distinct from most growth factors, with the exception of the epidermal growth factor/transforming growth factor-␣ family (13). In addition to the mammalian granulins of human (1,6), rat (2,12), mouse (10,15), and horse (16), granulin-like proteins have been identified in a number of non-mammalian organisms including the nematode Caenorhabditis elegans (17), the locust (18), the mussel (19), the marine worm Hediste diversicolor (20), and teleosts (bony fish) (21)(22)(23). Granulin-like motifs have also been identified in multiple thiol protease gene sequences from plants (24,25).…”

The granulin gene family: from cancer to dementia

“…The mammalian GRN gene encodes a multifunctional secreted glycoprotein with tandem repeats of cysteine-rich GRN modules (1,(36)(37)(38)(39) (Fig. 1A).…”

“…1A). It is known synonymously as PGRN, (8) granulin-epithelin precursor (GEP), (40) proepithelin, (38) PC cell-derived growth factor (PCDGF), (10) acrogranin, (39) and epithelial transforming growth factor (TGFe). (41) This rather dense nomenclature for a single gene is revealing since it captures many of the essential features of the biology of PGRN.…”