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Novel function of SHANK3 on vascular inflammation
and atherosclerosis
Jinri Lee , Sanguk Yun *
¹
1
Department of biotechnology, Inje University, Gimhae-si 50834, Korea

Abstract Result

Shank protein constitutes PSD in neurons and is a A
scaffolding protein that interacts with various
proteins such as GPCR, neurotransmitter receptor,
and actin cytoskeleton. In addition to neurons, it is
expressed in many other tissues such as the
intestine, breast, kidney, and vasculature, and has
been shown to function as a signal transducer in
multiple cell types. Recently, we investigated the
effect of extracellular matrix (ECM) proteins on
disturbed flow-induced phospho-proteome and B * *
identified Shank3 as a PP2A target whose
phosphorylation decreased on fibronectin, a pro-
Shank protein constitutes PSD in neurons and is a
inflammatory ECM. Interestingly, Shank3 deficiency
showed an increase in flow-induced inflammation
scaffolding protein that interacts with various proteins such
in endothelial cells. Therefore, we suggest a novel
as GPCR, neurotransmitter receptor, and actin cytoskeleton.
function of Shank3 on vascular inflammation and
atherosclerosis.
In addition to neurons, it is expressed in many other tissues
Introduction
such as the intestine, breast, kidney and vasculature, and
Fig 1. SHANK3 deficiency leads to increased inflammation in
the disturbed flow. (A) and (B), Disturbed flow in endothelial
has been shown to function as signal transducer in multiple
cells increases YAP (p=0.0943) and p65(p=0.07978).
cell types. Recently, we investigated the effect of
extracellular matrix (ECM) proteins on disturbed flow-
Conclusion
induced phospho-proteome and identified Shank3 as a
Shank3 was identified as a scaffolding protein
•
PP2A target whose phosphorylation decreased on
regulated by ECM-dependent phosphorylation
in endothelial cells. In an in vitro disturbed flow
fibronectin, a pro-inflammatory ECM. Interestingly, Shank3
environment, Shank3 Knockdown cells showed
activation of the inflammatory genes NF-kB and
knockout showed a decrease in flow-induced inflammation
YAP. therefore, we suggest that shank3 may be
used
an
inflammatory
modulator
in
as
in endothelial cells. Therefore, we suggest a novel function
atherosclerosis.
of Shank3 on vascular inflammation and atherosclerosis.
References
Method (1) Lilja, J., Zacharchenko, T., Georgiadou, M. et
al. SHANK proteins limit integrin activation by directly
interacting with Rap1 and R-Ras. Nat Cell
- Western blot Biol 19, 292–305 (2017).
- Shear stress (2) Singh B, Kosuru R, Lakshmikanthan S, Sorci-Thomas
Cells were starved in DMEM containing 1% FBS MG, Zhang DX, Sparapani R, Vasquez-Vivar J,
for 6 hours before applying shear stress. Cell Chrzanowska M. Endothelial Rap1 (Ras-Association
attachment was performed on glass slides Proximate 1) Restricts Inflammatory Signaling to
blocked with 0.2% BSA after Fibronectin coating Protect From the Progression of Atherosclerosis.
a then shear stress was applied± for 15 hours Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):638-
2
(1±5 dynes/cm , 37˚C) 650.