title: Coalignment of plasma membrane channels and protrusions (fibripositors) specifies the parallelism of tendon.
abstract: The functional properties of tendon require an extracellular matrix (ECM) rich in elongated collagen fibrils in parallel register. We sought to understand how embryonic fibroblasts elaborate this exquisite arrangement of fibrils. We show that procollagen processing and collagen fibrillogenesis are initiated in Golgi to plasma membrane carriers (GPCs). These carriers and their cargo of 28-nm-diam fibrils are targeted to previously unidentified plasma membrane (PM) protrusions (here designated "fibripositors") that are parallel to the tendon axis and project into parallel channels between cells. The base of the fibripositor lumen (buried several microns within the cell) is a nucleation site of collagen fibrillogenesis. The tip of the fibripositor is the site of fibril deposition to the ECM. Fibripositors are absent at postnatal stages when fibrils increase in diameter by accretion of extracellular collagen, thereby maintaining parallelism of the tendon. Thus, we show that the parallelism of tendon is determined by the late secretory pathway and interaction of adjacent PMs to form extracellular channels.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT UK.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Canty
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Lu
authors.forename: Roger S
authors.initials: RS
authors.lastname: Meadows
authors.forename: Michael K
authors.initials: MK
authors.lastname: Shaw
authors.forename: David F
authors.initials: DF
authors.lastname: Holmes
authors.forename: Karl E
authors.initials: KE
authors.lastname: Kadler
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D022081:Cell Surface Extensions / Q000378:metabolism* / Q000648:ultrastructure; D002642:Chick Embryo; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005333:Fetus; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D010455:Peptides / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D013710:Tendons / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D010455:Peptides; D011347:Procollagen; D003094:Collagen; D006735:Horseradish Peroxidase