Golgi-independent routes support protein disulfide isomerase externalization in vascular smooth muscle cells

Author(s)

Araujo, Thais L. S. ; Fernandes, Carolina G. ; Laurindo, Francisco R. M.

• Document type: Journal article
• Source: REDOX BIOLOGY; v. 12, p. 1004-1010, AUG 2017.
• Web of Science Citations: 3

Abstract

Extracellular pools of intracellular molecular chaperones are increasingly evident. The peri/epicellular(pec) pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1(PDI) is involved in thrombosis and vascular remodeling, while PDI externalization routes remain elusive. In endothelial cells, vesicular-type PDI secretion involves classical and unconventional pathways, while in platelets PDI exocytosis involves actin cytoskeleton. However, little is known about pecPDI in vascular smooth muscle cells(VSMC). Here, we showed that VSMC display a robust cell-surface(cs) PDI pool, which binds to cs independently of electrostatic forces. However, contrarily to other cells, soluble secreted PDI pool was undetectable in VSMC. Calcium ionophore A23187 and TNF alpha enhanced VSMC csPDI. Furthermore, VSMC PDI externalization occurred via Golgi-bypass unconventional route, which was independent of cytoskeleton or lysosomes. Secreted PDI was absent in ex vivo wild-type mice aortas but markedly enhanced in PDI-overexpressing mice. Such characterization of VSMC pecPDI reinforces cell-type and context specific routes of PDI externalization. (AU)

• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/02372-0 - Mechanisms and redox effects of epi/pericellular protein disulfide isomerase
• Grantee: Thaís Larissa Araujo de Oliveira Silva
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/06210-2 - Grasp pathway involving on the protein disulfide isomerase externalization and its implication in endothelial cell response
• Grantee: Thaís Larissa Araujo de Oliveira Silva
• Support type: Scholarships in Brazil - Post-Doctorate