title: Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility.
abstract: 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.
authors: Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States of America.
authors: Manik
authors: M
authors: Goel
authors: Adam E
authors: AE
authors: Sienkiewicz
authors: Renata
authors: R
authors: Picciani
authors: Richard K
authors: RK
authors: Lee
authors: Sanjoy K
authors: SK
authors: Bhattacharya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000378:metabolism*; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism*
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; C110668:COCH protein, human; D016326:Extracellular Matrix Proteins; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1