Peter Arvan
YOU?
Author Swipe
View article: Limiting ER-associated degradation capacity triggers acute and chronic effects on insulin biosynthesis
Limiting ER-associated degradation capacity triggers acute and chronic effects on insulin biosynthesis Open
In pancreatic β-cells, misfolded proinsulin is a substrate for Endoplasmic Reticulum-Associated protein Degradation (ERAD) via HRD1/SEL1L. β-cell HRD1 activity is alternately reported to improve, or impair, insulin biogenesis. Further, whi…
View article: Stimulated thyroid hormone synthesis machinery drives thyrocyte cell death independent of ER stress
Stimulated thyroid hormone synthesis machinery drives thyrocyte cell death independent of ER stress Open
It is now recognized that patients and animal models expressing genetically-encoded misfolded mutant thyroglobulin (TG, the protein precursor for thyroid hormone synthesis) exhibit dramatic swelling of the endoplasmic reticulum (ER) with E…
View article: SAT-393 Physiology Of A Thyroidally-Derived T3-Centric Hormonal Environment
SAT-393 Physiology Of A Thyroidally-Derived T3-Centric Hormonal Environment Open
Disclosure: C.E. Citterio: None. B. Morales-Rodriguez: None. X. Liao: None. C. Vu: None. R. Nguyen: None. J. Tsai: None. J. Le: None. I. Metawea: None. M. Liu: None. D.P. Olson: None. S. Refetoff: None. P. Arvan: None. Thyroid hormones (T4…
View article: Recessive TMEM167A variants cause neonatal diabetes, microcephaly, and epilepsy syndrome
Recessive TMEM167A variants cause neonatal diabetes, microcephaly, and epilepsy syndrome Open
Understanding the genetic causes of diseases that affect pancreatic β cells and neurons can give insights into pathways essential for both cell types. Microcephaly, epilepsy, and diabetes syndrome (MEDS) is a congenital disorder with two k…
View article: Thyroidal expression of ER molecular chaperone GRP170 is required for efficient TSH-mediated thyroid hormone synthesis
Thyroidal expression of ER molecular chaperone GRP170 is required for efficient TSH-mediated thyroid hormone synthesis Open
Intracellular trafficking of secretory and membrane proteins from the endoplasmic reticulum (ER) to the cell surface, via the secretory pathway, is crucial to the differentiated function of epithelial tissues. In the thyroid gland, a prere…
View article: A Genetically-Engineered Thyroid Gland Built for Selective Triiodothyronine Secretion
A Genetically-Engineered Thyroid Gland Built for Selective Triiodothyronine Secretion Open
Thyroid hormones (thyroxine, T4, and triiodothyronine, T3) are indispensable for sustaining vertebrate life, and their deficiency gives rise to a wide range of symptoms characteristic of hypothyroidism, affecting 5–10% of the world’s popul…
View article: Trapα deficiency impairs the early events of insulin biosynthesis and glucose homeostasis
Trapα deficiency impairs the early events of insulin biosynthesis and glucose homeostasis Open
Defects in the early events of insulin biosynthesis, including inefficient preproinsulin (PPI) translocation across the membrane of the ER and proinsulin (PI) misfolding in the ER, can cause diabetes. Cellular machineries involved in these…
View article: SEL1L-HRD1 ER-Associated Degradation Facilitates Prohormone Convertase 2 Maturation and Glucagon Production in Islet α Cells
SEL1L-HRD1 ER-Associated Degradation Facilitates Prohormone Convertase 2 Maturation and Glucagon Production in Islet α Cells Open
Proteolytic cleavage of proglucagon by prohormone convertase 2 (PC2) is required for islet α cells to generate glucagon. However, the regulatory mechanisms underlying this process remain largely unclear. Here, we report that SEL1L-HRD1 end…
View article: Small-Molecule FICD Inhibitors Suppress Endogenous and Pathologic FICD-Mediated Protein AMPylation
Small-Molecule FICD Inhibitors Suppress Endogenous and Pathologic FICD-Mediated Protein AMPylation Open
The AMP transferase, FICD, is an emerging drug target fine-tuning stress signaling in the endoplasmic reticulum (ER). FICD is a bifunctional enzyme, catalyzing both AMP addition (AMPylation) and removal (deAMPylation) from the ER-resident …
View article: Quantification of Folded and Misfolded Proinsulin Forms Using Nonreducing SDS-PAGE and Proinsulin-Specific Immunoblotting
Quantification of Folded and Misfolded Proinsulin Forms Using Nonreducing SDS-PAGE and Proinsulin-Specific Immunoblotting Open
We have observed that some proinsulin molecules in pancreatic islets and beta cell lines have incomplete or improper intramolecular disulfide bonds. These misfolded monomers can form intermolecular disulfide-linked complexes. Accurately qu…
View article: SIGMAR1/Sigma-1 receptor: a key regulator in stabilizing and translating <i>LC3B</i> mRNA for autophagosome formation
SIGMAR1/Sigma-1 receptor: a key regulator in stabilizing and translating <i>LC3B</i> mRNA for autophagosome formation Open
Macroautophagy/autophagy degrades and recycles cellular constituents via the lysosome to maintain cellular homeostasis. Our study identified the endoplasmic reticulum (ER)-resident SIGMAR1 (sigma non-opioid intracellular receptor 1) as a c…
View article: 7249 In Vivo Hormongenic Potential of the Thyroglobulin Cholinesterase-like (ChEL) Domain
7249 In Vivo Hormongenic Potential of the Thyroglobulin Cholinesterase-like (ChEL) Domain Open
Disclosure: C.E. Citterio: None. B. Morales-Rodriguez: None. P. Lee: None. R. Bhavana: None. M. Liu: None. D.P. Olson: None. X. Liao: None. S. Refetoff: None. P. Arvan: None. Vertebrate life is unsustainable without thyroid hormone. The on…
View article: Role of Sec61a2 translocon in insulin biosynthesis
Role of Sec61a2 translocon in insulin biosynthesis Open
AbstractTranslocational regulation of proinsulin biosynthesis in pancreatic b-cells is unknown, although several studies have reported an important accessory role for the Translocon-Associated Protein complex to assist preproinsulin delive…
View article: Role of Sec61α2 Translocon in Insulin Biosynthesis
Role of Sec61α2 Translocon in Insulin Biosynthesis Open
Translocational regulation of proinsulin biosynthesis in pancreatic β-cells is unknown, although several studies have reported an important accessory role for the Translocon-Associated Protein complex to assist preproinsulin delivery into …
View article: Sigma-1 receptor recruits LC3 mRNA to ER-associated omegasomes to promote localized LC3 translation enabling functional autophagy
Sigma-1 receptor recruits LC3 mRNA to ER-associated omegasomes to promote localized LC3 translation enabling functional autophagy Open
Autophagosome formation initiated on the endoplasmic reticulum (ER)-associated omegasome requires LC3. Translational regulation of LC3 biosynthesis is unexplored. Here we demonstrate that LC3 mRNA is recruited to omegasomes by directly bin…
View article: Small molecule FICD inhibitors suppress endogenous and pathologic FICD-mediated protein AMPylation
Small molecule FICD inhibitors suppress endogenous and pathologic FICD-mediated protein AMPylation Open
Summary The AMP transferase, FICD, is an emerging drug target finetuning stress signaling in the endoplasmic reticulum (ER). FICD is a bi-functional enzyme, catalyzing both AMP addition (AMPylation) and removal (deAMPylation) from the ER r…
View article: Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway
Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway Open
The integrated stress response (ISR) regulates cell fate during conditions of stress by leveraging the cell’s capacity to endure sustainable and efficient adaptive stress responses. Protein phosphatase 2A (PP2A) activity modulation has bee…
View article: Proinsulin folding and trafficking defects trigger a common pathological disturbance of endoplasmic reticulum homeostasis
Proinsulin folding and trafficking defects trigger a common pathological disturbance of endoplasmic reticulum homeostasis Open
Primary defects in folding of mutant proinsulin can cause dominant‐negative proinsulin accumulation in the endoplasmic reticulum (ER), impaired anterograde proinsulin trafficking, perturbed ER homeostasis, diminished insulin production, an…
View article: Permanent neonatal diabetes-causing insulin mutations have dominant negative effects on beta cell identity
Permanent neonatal diabetes-causing insulin mutations have dominant negative effects on beta cell identity Open
These results highlight a novel mechanism, the loss of beta cell identity, contributing to the loss and functional failure of human beta cells with specific insulin gene mutations.
View article: Autophagy of the <scp>ER</scp>: the secretome finds the lysosome
Autophagy of the <span>ER</span>: the secretome finds the lysosome Open
Lysosomal degradation of the endoplasmic reticulum (ER) and its components through the autophagy pathway has emerged as a major regulator of ER proteostasis. Commonly referred to as ER‐phagy and ER‐to‐lysosome‐associated degradation (ERLAD…
View article: OR14-01 Contact Between Thyroglobulin Opposite Domains Assists Its Upstream Regions In Intracellular Trafficking For Thyroid Hormonogenesis
OR14-01 Contact Between Thyroglobulin Opposite Domains Assists Its Upstream Regions In Intracellular Trafficking For Thyroid Hormonogenesis Open
Disclosure: C.E. Citterio: None. K. Kim: None. B. Rajesh: None. K. Pena: None. O.B. Clarke: None. P. Arvan: None. Thyroglobulin (Tg), must be released into the lumen of thyroid follicles to facilitate thyroid hormone synthesis. The Tg prim…
View article: Structural features of thyroglobulin linked to protein trafficking
Structural features of thyroglobulin linked to protein trafficking Open
Thyroglobulin must pass endoplasmic reticulum (ER) quality control to become secreted for thyroid hormone synthesis. Defective thyroglobulin, blocked in trafficking, can cause hypothyroidism. Thyroglobulin is a large protein (~2750 residue…
View article: Permanent Neonatal diabetes-causing Insulin mutations have dominant negative effects on beta cell identity
Permanent Neonatal diabetes-causing Insulin mutations have dominant negative effects on beta cell identity Open
Heterozygous coding sequence mutations of the INS gene are a cause of permanent neonatal diabetes (PNDM) that results from beta cell failure. We explored the causes of beta cell failure in two PNDM patients with two distinct INS mutations.…
View article: ER stress increases expression of intracellular calcium channel RyR1 to modify Ca2+ homeostasis in pancreatic beta cells
ER stress increases expression of intracellular calcium channel RyR1 to modify Ca2+ homeostasis in pancreatic beta cells Open
Pancreatic beta cells maintain glucose homeostasis by secreting pulses of insulin in response to a rise in plasma glucose. Pulsatile insulin secretion occurs as a result of glucose-induced oscillations in beta-cell cytosolic Ca. The endopl…
View article: Perturbation of endoplasmic reticulum proteostasis triggers tissue injury in the thyroid gland
Perturbation of endoplasmic reticulum proteostasis triggers tissue injury in the thyroid gland Open
Defects in endoplasmic reticulum (ER) proteostasis have been linked to diseases in multiple organ systems. Here we examined the impact of perturbation of ER proteostasis in mice bearing thyrocyte-specific knockout of either HRD1 (to disabl…