PATJ regulates cell stress responses and vascular remodeling post-stroke

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• PALS1-associated tight junction (PATJ) protein is implicated in metabolic disease and stroke.
• Its precise role in metabolic disease and ischemic stroke recovery is not well understood.
• PATJ is known to be involved in cell polarization.

Purpose of the Study:

• To investigate the functions of PATJ in vitro and in vivo.
• To explore PATJ's role in cellular processes relevant to stroke recovery.
• To understand PATJ's involvement in the Yes-associated protein (YAP)-1 signaling pathway.

Main Methods:

• Utilized CRISPR-Cas9 to generate PATJ knock-out (KO) HEK293 cells.
• Employed RNA sequencing for transcriptional analysis of PATJ KO cells.
• Used a mouse model of ischemic stroke and C. elegans for in vivo studies.
• Investigated PATJ homolog (mpz-1) function under hypoxic conditions in C. elegans.

Main Results:

• PATJ expression increased in endothelial cells post-ischemic stroke in mice.
• PATJ KO cells showed altered proliferation, migration, mitochondrial stress response, and YAP1 signaling.
• Transcriptional reprogramming in PATJ KO cells affected genes in vascular development, stress response, and metabolism.
• C. elegans PATJ homolog (mpz-1) knockdown exacerbated neuronal defects and mortality under hypoxia.

Conclusions:

• PATJ plays a significant role in cellular functions, including proliferation, migration, and stress response.
• PATJ is critical for maintaining neuronal integrity and survival, especially under hypoxic stress.
• These findings highlight PATJ as a potential therapeutic target for stroke rehabilitation and neurovascular repair.