Gene expression of the dibasic-pair cleaving enzyme NRD convertase (N-arginine dibasic convertase) is differentially regulated in the GH3 pituitary and Mat-Lu prostate cell lines

Winter, Andrew G.; Pierotti, Adrian R.

doi:10.1042/0264-6021:3510755

Cited by 6 publications

(3 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another explanation could be that Nardilysin is synthesized by the cells as a precursor or native form at this level, rendering it undetectable, and then the mature form can be present in the cytoplasm, more or less coupled with microtubules. Previous studies reported that Nardilysin is expressed at a time when transcriptional activity in the haploid germ cell nucleus has terminated [ 16 ]. Thus as reported for FS and ODF proteins corresponding to cytoskeletal adjuncts of the flagellum [ 44 , 45 ], it can be hypothesized that Nardilysin transcripts must first be stored in the spermatid before being translated.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ultrastructural localization and distribution of Nardilysin in mammalian male germ cells

Segretain

Gilleron

Bacro

et al. 2016

Basic Clin. Androl.

View full text Add to dashboard Cite

Background NRD convertase, also termed Nardilysin, is a Zn++ metalloendopeptidase that specifically cleaves the N-terminus of arginine and lysine residues into dibasic moieties. Although this enzyme was found located within the testis, its function in male reproduction is largely unknown. In addition, the precise distribution of this enzyme within germ cells remains to be determined. Methods To answer these questions, we developed an immuno-gold electron microscopy analysis to detect Nardilysin at ultrastructural level in mice. In addition, we performed a quantitative analysis of these gold particles to statistically estimate the distribution of Nardilysin in the different subcellular compartments of differentiating late spermatids/spermatozoa. Results Expression of Nardilysin in wild-type mice was restricted to germ cells and markedly increased during the last steps of spermiogenesis. In elongated spermatids, we found the enzyme mainly localized in the cytoplasm, more precisely associated with two microtubular structures, the manchette and the axoneme. No labelling was detected over the membranous organelles of the spermatids. To test whether this localization is dependent of the functional microtubules organization of the flagella, we analysed the localization into a specific mouse mutant ebo/ebo (ébouriffé) known to be sterile due to an impairment of the final organization of the flagellum. In the ebo/ebo, the enzyme was still localized over the microtubules of the axoneme and over the isolated cytoplasmic microtubules doublets. Quantification of gold particles in wild-type and mutant flagella revealed the specific association of the enzyme within the microtubular area of the axoneme. Conclusions The strong and specific accumulation of Nardilysin in the manchette and axoneme suggests that the enzyme probably contributes either to the establishment of these specific microtubular structures and/or to their functional properties.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Abundant in many endocrine tissues, Nardilysin was found in the testis [ 14 – 16 ], where high levels have been detected. Spermatogenesis is a complex process, which produces highly differentiated cells, the spermatozoa.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural localization and distribution of Nardilysin in mammalian male germ cells

Segretain

Gilleron

Bacro

et al. 2016

Basic Clin. Androl.

View full text Add to dashboard Cite

show abstract

“…Expression then appears in many other tissues but remains dominant in the nervous and urogenital systems [7]. In the adult mouse, NRDc is particularly abundant in heart, skeletal muscle and testis [7][8][9]. In the latter tissue, NRDc accumulates in elongated spermatids where it is associated with the microtubular structure of the flagellum [5].…”

Section: Introductionmentioning

confidence: 99%

The metalloendopeptidase nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF)

Nishi

Klagsbrun

Cohen

et al. 2002

Biochemical Journal

View full text Add to dashboard Cite

Nardilysin (N-arginine dibasic convertase, or NRDc) is a cytosolic and cell-surface metalloendopeptidase that, in vitro, cleaves substrates upstream of Arg or Lys in basic pairs. NRDc differs from most of the other members of the M16 family of metalloendopeptidases by a 90 amino acid acidic domain (DAC) inserted close to its active site. At the cell surface, NRDc binds heparin-binding epidermal growth factor-like growth factor (HB-EGF) and enhances HB-EGF-induced cell migration. An active-site mutant of NRDc fulfills this function as well as wild-type NRDc, indicating that the enzyme activity is not required for this process. We now demonstrate that NRDc starts at Met(49). Furthermore, we show that HB-EGF not only binds to NRDc but also potently inhibits its enzymic activity. NRDc-HB-EGF interaction involves the 21 amino acid heparin-binding domain (P21) of the growth factor, the DAC of NRDc and most probably its active site. Only disulphide-bonded P21 dimers are inhibitory. We also show that Ca(2+), via the DAC, regulates both NRDc activity and HB-EGF binding. We conclude that the DAC is thus a key regulatory element for the two distinct functions that NRDc fulfills, i.e. as an HB-EGF modulator and a peptidase.

show abstract

Metalloproteases and Metalloprotease Inhibitors

Gupta

2005

Proteomics of Spermatogenesis

View full text Add to dashboard Cite

Gene expression of the dibasic-pair cleaving enzyme NRD convertase (N-arginine dibasic convertase) is differentially regulated in the GH3 pituitary and Mat-Lu prostate cell lines

Cited by 6 publications

References 36 publications

Ultrastructural localization and distribution of Nardilysin in mammalian male germ cells

Ultrastructural localization and distribution of Nardilysin in mammalian male germ cells

The metalloendopeptidase nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF)

Metalloproteases and Metalloprotease Inhibitors

Contact Info

Product

Resources

About