Reference Report

Reference
Citation	Osterwalder, T., Kuhnen, A., Leiserson, W.M., Kim, Y.S., Keshishian, H. (2004). Drosophila serpin 4 functions as a neuroserpin-like inhibitor of subtilisin-like proprotein convertases. J. Neurosci. 24(24): 5482--5491. (Export to RIS)
FlyBase ID	FBrf0179368
Publication Type	Research paper
PubMed ID	15201320
PubMed Abstract	The proteolytic processing of neuropeptide precursors is believed to be regulated by serine proteinase inhibitors, or serpins. Here we describe the molecular cloning and functional expression of a novel member of the serpin family, Serine protease inhibitor 4 (Spn4), that we propose is involved in the regulation of peptide maturation in Drosophila. The Spn4 gene encodes at least two different serpin proteins, generated by alternate splicing of the last coding exon. The closest vertebrate homolog to Spn4 is neuroserpin. Like neuroserpin, one of the Spn4 proteins (Spn4.1) features a unique C-terminal extension, reminiscent of an endoplasmic reticulum (ER) retention signal; however, Spn4.1 and neuroserpin have divergent reactive site loops, with Spn4.1 showing a generic recognition site for furin/SPC1, the founding member of the intracellularly active family of subtilisin-like proprotein convertases (SPCs). In vitro, Spn4.1 forms SDS-stable complexes with the SPC furin and directly inhibits it. When Spn4.1 is overexpressed in specific peptidergic cells of Drosophila larvae, the animals exhibit a phenotype consistent with disrupted neuropeptide processing. This observation, together with the unique combination of an ER-retention signal, a target sequence for SPCs in the reactive site loop, and the in vitro inhibitory activity against furin, strongly suggests that Spn4.1 is an intracellular regulator of SPCs.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	J. Neurosci.
Title	Journal of Neuroscience
Publication Year	1981-
ISBN/ISSN	0270-6474 1529-2401
Data from Reference
Alleles (8)
	Avic\GFP^{2x.EGFP.Scer\UAS} ETH^{T:Avic\GFP-EGFP} Ggal\SerpinI1^Scer\UAS.cOa Scer\GAL4^dimm-929 Scer\GAL4^how-24B Spn27A^Scer\UAS.cOa Spn42Da^4.1.Scer\UAS Spn42Da^4.2.Scer\UAS
Constructs (6)
	P{ETH.3.egfp} P{UAS-2xEGFP} P{UAS-Neus.O} P{UASp-Spn4.1} P{UASp-Spn4.2} P{UAS-Spn27A.O}
Genes (7)
	Avic\GFP ETH eve Ggal\SerpinI1 Scer\GAL4 Spn27A Spn42Da
Insertions (4)
	P{GawB}dimm⁹²⁹ P{GawB}how^24B P{UASp-Spn4.1}282 P{UASp-Spn4.1}283
Natural transposons (1)
	P-element