ArticleMolecular and cellular biology2016
Dissection of Thrombospondin-4 Domains Involved in Intracellular Adaptive Endoplasmic Reticulum Stress-Responsive Signaling.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
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- Rab3gap1 palmitoylation cycling modulates cardiomyocyte exocytosis and atrial natriuretic peptide release.Biophysical journal · 2025Article
- zDHHC9 Regulates Cardiomyocyte Rab3a Activity and Atrial Natriuretic Peptide Secretion Through Palmitoylation of Rab3gap1.JACC. Basic to translational science · 2023Article
- Ankyrin-B is lipid-modified byFrontiers in physiology · 2023Article
- Collagen VII maintains proteostasis in dermal fibroblasts by scaffolding TANGO1 cargo.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Thbs1 induces lethal cardiac atrophy through PERK-ATF4 regulated autophagy.Nature communications · 2021Article
- Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of Adult Neurogenesis.Cell stem cell · 2020Article
- Effects of thrombospondin-4 on pro-inflammatory phenotype differentiation and apoptosis in macrophages.Cell death & disease · 2020Article
- Disruption of valosin-containing protein activity causes cardiomyopathy and reveals pleiotropic functions in cardiac homeostasis.The Journal of biological chemistry · 2019Article
- Cardiac Muscle Membrane Stabilization in Myocardial Reperfusion Injury.JACC. Basic to translational science · 2019Review
- Overlapping and differential functions of ATF6α versus ATF6β in the mouse heart.Scientific reports · 2019Article
- Thrombospondin-3 augments injury-induced cardiomyopathy by intracellular integrin inhibition and sarcolemmal instability.Nature communications · 2019Article
- Defective Flux of Thrombospondin-4 through the Secretory Pathway Impairs Cardiomyocyte Membrane Stability and Causes Cardiomyopathy.Molecular and cellular biology · 2018Article
- Thrombospondins: Purification of human platelet thrombospondin-1.Methods in cell biology · 2018Article
- Thrombospondins: A Role in Cardiovascular Disease.International journal of molecular sciences · 2017Review
- Article
- GRP78 Interacting Partner Bag5 Responds to ER Stress and Protects Cardiomyocytes From ER Stress-Induced Apoptosis.Journal of cellular biochemistry · 2016Article
- Reciprocal regulation of long noncoding RNAs THBS4‑003 and THBS4 control migration and invasion in prostate cancer cell lines.Molecular medicine reports · 2016Article
- LRRC10 is required to maintain cardiac function in response to pressure overload.American journal of physiology. Heart and circulatory physiology · 2016Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Thrombospondins are a family of stress-inducible secreted glycoproteins that underlie tissue remodeling. We recently reported that thrombospondin-4 (Thbs4) has a critical intracellular function, regulating the adaptive endoplasmic reticulum (ER) stress pathway through activating transcription factor 6α (Atf6α). In the present study, we dissected the domains of Thbs4 that mediate interactions with ER proteins, such as BiP (Grp78) and Atf6α, and the domains mediating activation of the ER stress response. Functionally, Thbs4 localized to the ER and post-ER vesicles and was actively secreted from cardiomyocytes, as were the type III repeat (T3R) and TSP-C domains, while the LamG domain localized to the Golgi apparatus. We also mutated the major calcium-binding motifs within the T3R domain of full-length Thbs4, causing ER retention and secretion blockade. The T3R and TSP-C domains as well as wild-type Thbs4 and the calcium-binding mutant interacted with Atf6α, induced an adaptive ER stress response, and caused expansion of intracellular vesicles. In contrast, overexpression of a related secreted oligomeric glycoprotein, Nell2, which lacks only the T3R and TSP-C domains, did not cause these effects. Finally, deletion of Atf6α abrogated Thbs4-induced vesicular expansion. Taken together, these data identify the critical intracellular functional domains of Thbs4, which was formerly thought to have only extracellular functions.
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