GlyCosmos Portal

Submissions

Mechanical load activates signaling by PIEZO1 and integrins in osteocytes

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9856532

PubChem

R-HSA-9856532

Description

Osteocytes are mechanosensory cells in mineralized bone that have dendrites extending through lacunae (parallel with collagen fibers) and canaliculi (perpendicular to collagen fibers) to make contact with other osteocytes and with osteoblasts on the bone surface (reviewed in Moriishi and Komori 2022). Fluid flow and pressure in the lacunae and canaliculi are sensed by the dendrites and communicated to the cell body (inferred from mouse osteocytes in Burra et al. 2010), resulting in secretion of anabolic factors such as prostaglandin E2 (PGE2) that act to strengthen the bone (Siller-Jackson et al. 2008, Riquelme et al. 2021, reviewed in Zhao et al. 2023).
Mechanosensitive PIEZO1 channels are opened by membrane stretch and transport calcium and sodium ions along their concentration gradients into the osteocyte. T-type voltage-sensitive calcium channels (CaV2 channles) open secondarily and augment the calcium influx. Cytosolic calcium activates Pannexin-1 (PANX1) channels, which transport ATP from the cytosol to the extracellular region. Extracellular ATP binds P2RX7 (P2X7) receptors located in a complex with PANX1. P2RX7 then transports cations including calcium into the cell and may act in an autocrine and paracrine manner to propagate waves of calcium influx.
Integrin alphaV:beta3 (ITGAV:ITGB3) located in the plasma membrane of dendrites binds the extracellular matrix of the lacunar or canicular wall. Fluid flow activates ITGAV:ITGB3 to phosphorylate AKT1 via a PI3K-dependent mechanism (Riquelme et al. 2021). Phospho-AKT1 then phosphorylates integrin alpha5 (ITGA5) and Connexin43 (GJA1) located in a complex in the plasma membrane of the cell body. Phospho-GJA1 transports ATP (Kang et al. 2008) and PGE2 from the cytosol to the extracellular region (reviewed in Zhao et al. 2023).
CaV3.2 voltage-sensitive calcium channels also directly interact with the extracellular proteoglycan perlecan (PLN, PLC, HSPG2) and the alpha2delta1 subunit of the CaV3.2 complex (Reyes Fernandez et al. 2022). Physical force on perlecan may thus affect calcium transport by the CaV3.2 channels.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 14 in total

1

2

Next ›

Last »
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O95180	Voltage-dependent T-type calcium channel subunit alpha-1H	CACNA1H	view
P05106	Integrin beta-3	GP3A ITGB3	view
P05556	Integrin beta-1	FNRB ITGB1 MDF2 MSK12	view
P06756	Integrin alpha-V	ITGAV MSK8 VNRA VTNR	view
P08648	Integrin alpha-5	FNRA ITGA5	view
P10451	Osteopontin	BNSP OPN PSEC0156 SPP1	view
P31749	RAC-alpha serine/threonine-protein kinase	AKT1 PKB RAC	view
P54289	Voltage-dependent calcium channel subunit alpha-2/delta-1	CACNA2D1 CACNL2A CCHL2A MHS3	view
P98160	Basement membrane-specific heparan sulfate proteoglycan core protein	HSPG2	view
Q02641	Voltage-dependent L-type calcium channel subunit beta-1	CACNB1 CACNLB1	view

Displaying 1 entry
GlyCosmos Lectin	UniProt ID	Lectin Name	Pathway Viewer
GL_005334	P98160	Basement membrane-specific heparan sulfate proteoglycan core protein	view

If you want to check the location of a particular molecule, you can do so by clicking on the "Switching Highlight" button on the page you have navigated to by clicking on "view".

About Release Notes Help Feedback

Click here to visit the beta site.