PT  - JOURNAL ARTICLE
AU  - Andrea Martello
AU  - Angela Lauriola
AU  - David Mellis
AU  - Elisa Parish
AU  - John C Dawson
AU  - Lisa Imrie
AU  - Martina Vidmar
AU  - Noor Gammoh
AU  - Tijana Mitic
AU  - Mairi Brittan
AU  - Nicholas Mills
AU  - Neil O Carragher
AU  - Domenico D’Arca
AU  - Andrea Caporali
TI  - Trichoplein controls endothelial cell function by regulating autophagy
AID  - 10.1101/595702
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 595702
4099  - http://biorxiv.org/content/early/2019/04/04/595702.short
4100  - http://biorxiv.org/content/early/2019/04/04/595702.full
AB  - Autophagy is an essential cellular quality control process that emerged critical for vascular homeostasis. Here we describe, the role for Trichoplein (TCHP) protein in linking autophagy with endothelial cells (ECs) function. The depletion of TCHP in ECs impairs migration and sprouting. TCHP directly binds PCM1, to regulate degradation of GABARAP, thus leading to a defective autophagy. Mechanistically, TCHP is indispensable for autophagosome maturation and its depletion resulted in the accumulation of SQSTM1/p62 (p62) and unfolded protein aggregates in ECs. The latter process is coupled to TCHP-mediated NF-kB activation. Of note, low levels of TCHP and high p62 levels were detected in primary ECs from patients with coronary artery disease. In addition, Tchp knock-out mice showed accumulation of p62 in the heart and cardiac vessels and reduced cardiac vascularization. Here, we reveal an autophagy-mediated mechanism for TCHP down-regulation, which poses a plausible target for regulation of endothelial function.