Sept12 is a component of the mammalian sperm tail annulus

Abstract

Since their essential role in cytokinesis was first shown in yeast, the septins have been described to function in diverse cellular contexts. The members of this unique class of GTPases are capable of binding and hydrolyzing GTP, associating with membranes and oligomerizing into higher order structures. Here we describe Sept12, a novel septin, identified in a yeast two hybrid screen using Sept5 as the bait. Sept12 contains the primary sequence elements of a septin and is capable of interacting with other septins. In addition, Sept12 purifies with bound nucleotide and binds to phosphoinositides, confirming its identity as a septin. RT-PCR and Northern blots reveal that Sept12 mRNA is expressed predominantly in testis, and this is supported by tissue Western blots. In rats, Sept12 protein levels rise upon sexual maturity and the Sept12 protein colocalizes with the annulus in isolated mature spermatozoa. Further, coexpression of Sept12 with Sept4, an essential annulus component, results in complete colocalization of both proteins into robust and highly curved filaments in CHO cells. This study suggests Sept12 may be involved in mammalian fertility.

The expression pattern of SEPT7 correlates with sperm morphology

“…Other proteins located at the mouse sperm annulus include DNAJB13 [24] and testis anion transporter 1 (TAT1) [25]. In the mouse, gene targeting of Septin4, Septin12, and Tat1 lead to abnormal mitochondrial organization and tail defects [6,7,11,25]. In humans, absence of the annulus is associated with abnormal mitochondrial organization in poor-motility sperm [9].…”

“…Considering the high similarity of the expression patterns of SEPT4, SEPT7, and SEPT12, it is highly likely that the SEPT4/7/12 complex not only constitutes the structural basis of the annulus but also serves as a diffusion barrier between the various subcellular compartments of mammalian spermatozoa [6,11,35,36]. As alterations in the expression of one septin can lead to altered expression of other septins [5], the concomitant use of multiple markers (SEPT4 + SEPT7 + SEPT12) may be superior to any single marker as a sperm-quality index.…”

“…There is increasing evidence of the involvement of septins in the pathogenesis of various human diseases, including neoplasia, neurodegenerative conditions, infection, and infertility [1,[6][7][8]. Among the 14 septin family members, SEPT4 and SEPT12 play important roles in the differentiation of postmeiotic germ cells.…”

“…In humans, disorganized annulus/SEPTIN rings were identified in a subset of patients with asthenozoospermia [9,10]. SEPT12 is also a component of the sperm annulus [6]. To explore the role of SEPT12 in mammalian spermatogenesis, we knocked out the Septin12 gene in mouse ES cells via gene targeting.…”

SEPT7 (septin 7)

“…This protein has a role in ciliogenesis and collective cell movements. The GTPase domain of SEPT7 is unique as it contains a conserved sequence near its end -the Septin Unique Element (SUE) (Pan et al, 2007, Steels et al, 2007, Versele et al, 2004. SEPT7 has additional conserved elements that flank the GTPase domain.…”