Membrane Interactome of a Recombinant Fragment of Human Surfactant Protein D Reveals GRP78 as a Novel Binding Partner in PC3, a Metastatic Prostate Cancer Cell Line

Surfactant protein-D (SP-D), a member of the collectin family has been shown to induce apoptosis in cancer cells. SP-D is composed of an N-terminal collagen-like domain and a calcium-dependent carbohydrate recognition domain (CRD). Recently, we reported that a recombinant fragment of human SP-D (rfh...

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Published inFrontiers in immunology Vol. 11; p. 600660
Main Authors Thakur, Gargi, Sathe, Gajanan, Kundu, Indra, Biswas, Barnali, Gautam, Poonam, Alkahtani, Saad, Idicula-Thomas, Susan, Sirdeshmukh, Ravi, Kishore, Uday, Madan, Taruna
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 19.01.2021
Subjects
apoptosis
GRP78
Immunology
interactome analysis
prostate cancer
signaling
surfactant protein D
prostate cancer
signaling
innate immunity
GRP78
apoptosis
interactome analysis
surfactant protein D
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Summary:Surfactant protein-D (SP-D), a member of the collectin family has been shown to induce apoptosis in cancer cells. SP-D is composed of an N-terminal collagen-like domain and a calcium-dependent carbohydrate recognition domain (CRD). Recently, we reported that a recombinant fragment of human SP-D (rfhSP-D), composed of homotrimeric CRD region, induced intrinsic apoptotic pathway in prostate cancer cells. Here, we analyzed the membrane interactome of rfhSP-D in an androgen-independent prostate cancer cell line, PC3, by high resolution mass spectrometry and identified 347 proteins. Computational analysis of PPI network of this interactome in the context of prostate cancer metastasis and apoptosis revealed Glucose Regulated Protein of 78 kDa (GRP78) as an important binding partner of rfhSP-D. Docking studies suggested that rfhSP-D (CRD) bound to the substrate-binding domain of glycosylated GRP78. This was further supported by the observations that human recombinant GRP78 interfered with the binding of rfhSP-D to anti-SP-D polyclonal antibodies; GRP78 also significantly inhibited the binding of recombinant full-length human SP-D with a monoclonal antibody specific to the CRD in a dose-dependent manner. We conclude that the interaction with rfhSP-D is likely to interfere with the pro-survival signaling of GRP78.
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This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
Edited by: Jagadeesh Bayry, Institut National de la Santé et de la Recherche Médicale (INSERM), France
Reviewed by: Umakhanth Venkatraman Girija, De Montfort University, United Kingdom; Nithyananda Thorenoor, Pennsylvania State University, United States
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2020.600660