Dataset Information

PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis

ABSTRACT: The formation of elastic fibers is active only in the perinatal period. How elastogenesis is developmentally regulated is not fully understood. Citrullination is a unique form of post-translational modification catalyzed by peptidylarginine deiminases (PADIPADs), including PADIPAD1-4. Its physiological role is largely unknown. By using an unbiased proteomic approach of lung tissues, we discovered that FBLN5 and LTBP4, two key elastogenic proteins, were temporally modified in mouse and human lungs. We further demonstrated that PADIPAD2 citrullinated FBLN5 preferentially in young lungs compared to adult lungs. Genetic ablation of PADIPAD2 resulted in attenuated elastogenesis in vitro and age-dependent emphysema in vivo. Mechanistically, citrullination protected FBLN5 from proteolysis and subsequent inactivation of its elastogenic activity. Furthermore, citrullinated but not native FBLN5 partially rescued in vitro elastogenesis in the absence of PADIPAD activity. Our data uncover a novel function of citrullination, namely promoting elastogenesis, and provide additional insights to how elastogenesis is regulated.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung

SUBMITTER: Paul Thompson

LAB HEAD: Paul Thompson

PROVIDER: PXD026238 | Pride | 2021-07-22

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	20200728_QE_Thompson_Tilvawala_HEK_1.msf	Msf
	20200728_QE_Thompson_Tilvawala_HEK_1.raw	Raw
	DTASelect-filter_old1.txt	Txt
	DTASelect-filter_old12.txt	Txt
	DTASelect-filter_old2.txt	Txt

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Publications

PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis.

Sun Bo B Tomita Beverly B Salinger Ari A Tilvawala Ronak R RR Li Ling L Hakami Hana H Liu Tao T Tsoyi Konstantin K Rosas Ivan O IO Reinhardt Dieter P DP Thompson Paul R PR Ho I-Cheng IC

Matrix biology : journal of the International Society for Matrix Biology 20210715

The formation of elastic fibers is active only in the perinatal period. How elastogenesis is developmentally regulated is not fully understood. Citrullination is a unique form of post-translational modification catalyzed by peptidylarginine deiminases (PADs), including PAD1-4. Its physiological role is largely unknown. By using an unbiased proteomic approach of lung tissues, we discovered that FBLN5 and LTBP4, two key elastogenic proteins, were temporally modified in mouse and human lungs. We fu ...[more]

PMID: 34274450

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