Basic fibroblast growth factor: an extracellular mechanotransducer in articular cartilage?

2006 ◽  
Vol 34 (3) ◽  
pp. 456-457 ◽  
Author(s):  
T. Vincent ◽  
J. Saklatvala

Mechanical stimuli are important signals in articular cartilage, but what mediates them is unknown. We have shown that extracellular-signal-regulated kinase was activated on cutting and loading articular cartilage, and deduced that this was due to the release of bFGF (basic fibroblast growth factor) from the tissue. bFGF was shown to be extracellular, and by immunohistochemistry, was present in the pericellular matrix of articular chondrocytes attached to the heparan sulphate proteoglycan perlecan. We propose a novel mechanotransduction model, whereby pericellular bFGF, a short distance from the cell surface, becomes available to the cell surface tyrosine kinase receptors when articular cartilage is loaded.

2021 ◽  
Author(s):  
Song Xue ◽  
Fan Zhou ◽  
Tian Zhao ◽  
Huimin Zhao ◽  
Xuewei Wang ◽  
...  

Liquid-liquid phase separation (LLPS) driven by weak, multivalent interactions among biomolecules is an important means of cellular compartmentation and plays a central role in cellular processes including stress resistance, RNA processing and other cellular activities. Coordination of the condensates and inner membrane was recently revealed, mediating intracellular processes like cell signalling and cargo trafficking. Intracellular LLPS has been observed extensively in vivo, whereas LLPS in extracellular compartments has not been reported under physiological conditions. Here we show, for the first time, that basic fibroblast growth factor (bFGF) undergoes LLPS on the cell surface by interacting with heparan sulphate proteoglycans (HSPG) and the phase transition is required for effective downstream signalling. The condensation is driven by multivalent interactions between bFGF and sulpho- groups on heparan sulphate (HS), and dimerization and oligomerization of bFGF promote the LLPS process. Compared with free bFGF, phase separated bFGF with HS showed higher thermo stability, providing a potential mechanism for the preservation of bFGF activity. Furthermore, we have found that downstream signalling is triggered by phase separation of a ternary complex formed by bFGF, HSPGs and FGFR on cell surface. Our results revealed a molecular mechanism that HS can serve as a platform to promote extracellular proteins like bFGF to condensate on outer membrane, consequently coordinating the signal transduction activities. This novel finding expands the horizons of phase separation in vivo, providing a new dimension on how HSPG may regulate extracellular protein behaviour and cell signalling.


1999 ◽  
Vol 338 (3) ◽  
pp. 637 ◽  
Author(s):  
Nicholas N. NISSEN ◽  
Ravi SHANKAR ◽  
Richard L. GAMELLI ◽  
Ashok SINGH ◽  
Luisa A. DIPIETRO

1996 ◽  
Vol 14 (2) ◽  
pp. 265-272 ◽  
Author(s):  
Jun-Ichi Shida ◽  
Seiya Jingushi ◽  
Toshihiro Izumi ◽  
Akira Iwaki ◽  
Yoichi Sugioka

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