Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States of America.
PLoS One. 2011;6(8):e23070. doi: 10.1371/journal.pone.0023070. Epub 2011 Aug 23.
Fluid flow through large interstitial spaces is sensed at the cellular level, and mechanistic responses to flow changes enables expansion or contraction of the cells modulating the surrounding area and brings about changes in fluid flow. In the anterior eye chamber, aqueous humor, a clear fluid, flows through trabecular meshwork (TM), a filter like region. Cochlin, a secreted protein in the extracellular matrix, was identified in the TM of glaucomatous patients but not controls by mass spectrometry. Cochlin undergoes shear induced multimerization and plays a role in mechanosensing of fluid shear. Cytoskeletal changes in response to mechanosensing in the ECM by cochlin will necessitate transduction of mechanosensing. TREK-1, a stretch activated outward rectifying potassium channel protein known to act as mechanotransducer was found to be expressed in TM. Cochlin expression results in co-expression of TREK-1 and filopodia formation. Prolonged cochlin expression results in expression and subsequent secretion of annexin A2, a protein known to play a role in cytoskeletal remodeling. Cochlin interacts with TREK-1 and annexin A2. Cochlin-TREK-1 interaction has functional consequences and results in changes in cell shape and motility. Annexin A2 expression and secretion follows cochlin-TREK-1 syn-expression and correlates with cell elongation. Thus cytoskeleton changes in response to fluid shear sensed by cochlin are further mediated by TREK-1 and annexin A2.
液体通过大的细胞间隙的流动在细胞水平被感知，并且对流动变化的机械响应使细胞扩张或收缩，从而调节周围区域并引起流体流动的变化。在前房，房水，一种清澈的液体，通过小梁网（TM），一个类似过滤器的区域流动。胶原，一种在青光眼患者 TM 中通过质谱鉴定的细胞外基质中的分泌蛋白，但在对照组中没有。胶原经历剪切诱导的多聚化，并在流体剪切的机械感觉中起作用。对细胞外基质中胶原的机械感觉的细胞骨架变化将需要机械感觉的转导。TREK-1，一种已知作为机械转导体的伸展激活的外向整流钾通道蛋白，在 TM 中被发现表达。胶原的表达导致 TREK-1 的共表达和丝状伪足的形成。胶原的长期表达导致 annexin A2 的表达和随后的分泌，已知 annexin A2 在细胞骨架重塑中起作用。胶原与 TREK-1 和 annexin A2 相互作用。胶原-TREK-1 相互作用具有功能后果，并导致细胞形状和运动性的变化。 annexin A2 的表达和分泌遵循 cochlin-TREK-1 共表达，并与细胞伸长相关。因此，胶原感知流体剪切引起的细胞骨架变化进一步由 TREK-1 和 annexin A2 介导。
