2026-05-22T00:30:16Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/267982025-12-18T13:01:53Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Sánchez-Álvarez, Miguel author Lolo, Fidel Nicolás author Sailem, Heba author Fulgoni, Giulio author Pascual-Vargas, Patricia author Agüera, Lucía author Catalá-Montoro, Mauro author Arias-García, Mar author López, Juan Antonio author Vázquez, Jesús author Del Pozo, Miguel Ángel author Bakal, Chris author 2025-05-27 The architecture of the endoplasmic reticulum (ER) is a key determinant of its function. Its dynamics are linked to those of the cytoskeleton, but our understanding of how this coordination occurs and what its functional relevance is, limited. Here, we report that the unfolded protein response (UPR) transducer EIF2AK3/PERK (eukaryotic translation initiation factor 2-alpha kinase 3/protein kinase R-like endoplasmic reticulum kinase) is essential for acute-stress-induced peripheral redistribution and remodeling of the ER through eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation and translation initiation shutdown. PERK-mediated eIF2α phosphorylation can be bypassed by blocking polysome assembly, depleting microtubule (MT)-anchoring ER proteins such as p180/RRBP1 (ribosome-binding protein 1), or disrupting the MT cytoskeleton. Specific disruption of non-centrosomal MTs, but not centrosome depletion, rescues ER redistribution in PERK-deficient cells. Conversely, PERK deficiency stabilizes non-centrosomal MTs against proteasomal degradation, promoting polarized protrusiveness in epithelial cells and neuroblasts. Thus, PERK coordinates ER architecture and homeostasis with cell morphogenesis by coupling ER remodeling and non-centrosomal MT stability and dynamics. Cell Rep. 2025 May 27;44(5):115590. Cell Reports 40267909 https://hdl.handle.net/20.500.12105/26798 CP: Cell biology EIF2AK3/PERK cell polarity endoplasmic reticulum integrated stress response non-centrosomal microtubules PERK-dependent reciprocal crosstalk between ER and non-centrosomal microtubules coordinates ER architecture and cell shape.