Immunohistochemical distribution of the prohormone convertase PC5-A in rat brain

Villeneuve, Pierre; Seidah, Nabil G.; Beaudet, Alain

doi:10.1016/s0306-4522(98)00763-5

Cited by 23 publications

(21 citation statements)

References 48 publications

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“…The distribution pattern of PC5-A in frog exhibits obvious similarities with that previously reported in mammals (Dong et al, 1995;Villeneuve et al, 1999). For instance, in frog and rat, high levels of PC5-A mRNA occur in the mitral cell layer of the olfactory bulb, in the diagonal band of Broca, and in various hypothalamic and thalamic nuclei (Dong et al, 1995).…”

Section: Distribution Of Frog Pc5-a Mrnasupporting

confidence: 78%

Molecular characterization of the cDNA and localization of the mRNA encoding the prohormone convertase PC5‐A in the European green frog

Gangnon

Jégou

Vallarino

et al. 2002

J of Comparative Neurology

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The structure and distribution of PC5-A, a prohormone convertase that is thought to be involved in post-translational processing of peptide hormone and neuropeptide precursors, have not been investigated in submammalian vertebrates. In the present study, we characterized the cDNA encoding PC5-A in the European green frog Rana esculenta. The frog PC5-A cDNA encodes a 913-amino acid protein that encompasses a 28-amino acid signal peptide, the Asp/His/Ser catalytic triad found in all serine proteinases of the subtilisin family, and two potential N-linked glycosylation sites located in a C-terminal cysteine-rich domain. Reverse transcriptase polymerase chain reaction amplification showed that PC5-A mRNA is expressed in various organs including the brain, spinal cord, pituitary, lung, liver, intestine, and testis, but not in the stomach and pancreas. The distribution of PC5-A mRNA in the frog brain was studied by in situ hybridization histochemistry. Intense expression was observed in the mitral cellular layer of the olfactory bulb, the nucleus of the diagonal band of Broca, the anterior preoptic area, and the suprachiasmatic and ventral hypothalamic nuclei. The expression pattern of PC5-A mRNA in the central nervous system of anuran amphibians was consistent with the implication of this prohormone convertase in the processing of various neuropeptide precursors.

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Section: Distribution Of Frog Pc5-a Mrnasupporting

confidence: 78%

Molecular characterization of the cDNA and localization of the mRNA encoding the prohormone convertase PC5‐A in the European green frog

Gangnon

Jégou

Vallarino

et al. 2002

J of Comparative Neurology

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“…In contrast to furin, PC5A expression is restricted to neurons (53), as has been shown for L1 (for review, see Ref. 20).…”

Section: Discussionmentioning

confidence: 81%

“…The particular spatial and temporal expression patterns of PC5A in the brain (45,52,53) overlap with those of L1 (54), whereas furin is ubiquitously expressed in all brain areas and cell types (55). In contrast to furin, PC5A expression is restricted to neurons (53), as has been shown for L1 (for review, see Ref.…”

Section: Discussionmentioning

confidence: 88%

The Proprotein Convertase PC5A and a Metalloprotease Are Involved in the Proteolytic Processing of the Neural Adhesion Molecule L1

Kalus

Schnegelsberg

Seidah

et al. 2003

Journal of Biological Chemistry

112

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The transmembrane and multidomain neural adhesion molecule L1 plays important functional roles in the developing and adult nervous system. L1 is proteolytically processed at two distinct sites within the extracellular domain, leading to the generation of different fragments. In this report, we present evidence that the proprotein convertase PC5A is the protease that cleaves L1 in the third fibronectin type III domain, whereas the proprotein convertases furin, PC1, PC2, PACE4, and PC7 are not effective in cleaving L1. Analysis of mutations revealed Arg 845 to be the site of cleavage generating the N-terminal 140-kDa fragment. This fragment was present in the hippocampus, which expresses PC5A, but was not detectable in the cerebellum, which does not express PC5A. The 140-kDa L1 fragment was found to be tightly associated with the full-length 200-kDa L1 molecule. The complex dissociated from the membrane upon cleavage by a protease acting at a more membrane-proximal site of full-length L1. This proteolytic cleavage was inhibited by the metalloprotease inhibitor GM 6001 and enhanced by a calmodulin inhibitor. L1-dependent neurite outgrowth of cerebellar neurons was inhibited by GM 6001, suggesting that proteolytic processing of L1 by a metalloprotease is involved in neurite outgrowth.Proteolytic processing of cell-surface proteins is of prime importance for regulating the functional properties of these proteins (for reviews, see Refs. 1-5). Cleavage of recognition molecules at the cell surface has been implicated in neuronal migration, neurite outgrowth, and synaptic plasticity (6 -13). Among the neural adhesion molecules, L1 has been shown to undergo proteolytic cleavage, which has been suggested to be involved in several functions of this molecule.L1 is a member of the immunoglobulin superfamily consisting of immunoglobulin-like domains and fibronectin type III repeats (for reviews, see Refs. 14 and 15). In the central nervous system, L1 is expressed only by post-mitotic neurons and mainly on non-myelinated axons, whereas in the peripheral nervous system, it is expressed by neurons as well as by non-myelinating Schwann cells. L1 is also expressed by nonneural cells, including normal and transformed cells of hematopoietic and epithelial origin. L1 is involved in neuronal migration, neurite outgrowth, and myelination (for review, see Ref. 14) as well as axon guidance, fasciculation, and regeneration (16,17). Furthermore, it enhances cell survival (18) and synaptic plasticity (19). The importance of L1 in nervous system development is underscored by the abnormal phenotypes of L1 mutations in humans and mice (for review, see Ref. 20). L1 engages in homophilic and heterophilic cell interactions (for reviews, see Refs. 14 and 15) Heterophilic binding partners are the RGD-binding integrins and TAG-1/ axonin-1, F3/F11/contactin, NCAM, CD9, CD24, and phosphacan (Ref. 21 and references therein). These interactions are likely to depend on the presentation of the L1 molecule either as a membrane-bound form or as a proteolytic...

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“…This idea has been in abeyance, but has substantial merit as the putative cleavage enzymes are widely expressed (Villeneuve et al 1999, Stawowy et al 2001, Cain et al 2003, Veinot et al 2004, under the influence of various physiological and pathological stimuli (Stawowy et al 2001, Veinot et al 2004, Marchesi et al 2011. Under this circumstance, the AMH N,C in circulation defines a basal level of activation, which can be amplified by the local cleavage of proAMH to AMH N,C .…”

Section: Extra-gonadal Cleavage Of Proamhmentioning

confidence: 99%

Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions

McLennan¹,

Pankhurst²

2015

Journal of Endocrinology

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Anti-Mü llerian hormone (AMH) is a multi-faceted gonadal cytokine. It is present in all vertebrates with its original function in phylogeny being as a regulator of germ cells in both sexes, and as a prime inducer of the male phenotype. Its ancient functions appear to be broadly conserved in mammals, but with this being obscured by its overt role in triggering the regression of the Mü llerian ducts in male embryos. Sertoli and ovarian follicular cells primarily release AMH as a prohormone (proAMH), which forms a stable complex (AMH N,C ) after cleavage by subtilisin/kexin-type proprotein convertases or serine proteinases. Circulating AMH is a mixture of proAMH and AMH N,C , suggesting that proAMH is activated within the gonads and putatively by its endocrine target-cells. The gonadal expression of the cleavage enzymes is subject to complex regulation, and the preliminary data suggest that this influences the relative proportions of proAMH and AMH N,C in the circulation. AMH shares an intracellular pathway with the bone morphogenetic protein (BMP) and growth differentiation factor (GDF) ligands. AMH is male specific during the initial stage of development, and theoretically should produce male biases throughout the body by adding a male-specific amplification of BMP/GDF signalling. Consistent with this, some of the male biases in neuron number and the non-sexual behaviours of mice are dependent on AMH. After puberty, circulating levels of AMH are similar in men and women. Putatively, the function of AMH in adulthood maybe to add a gonadal influence to BMP/GDF-regulated homeostasis.

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Immunohistochemical distribution of the prohormone convertase PC5-A in rat brain

Cited by 23 publications

References 48 publications

Molecular characterization of the cDNA and localization of the mRNA encoding the prohormone convertase PC5‐A in the European green frog

Molecular characterization of the cDNA and localization of the mRNA encoding the prohormone convertase PC5‐A in the European green frog

The Proprotein Convertase PC5A and a Metalloprotease Are Involved in the Proteolytic Processing of the Neural Adhesion Molecule L1

Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions

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