Transport of a hyaluronan-binding protein in brain tissue.
Hyaluronan is an unsulfated linear glycosaminoglycan with the ability to nucleate extracellular matrices by the formation of aggregates with lecticans. These matrices are essential during development of the central nervous system. In the prospective white matter of the developing brain hyaluronan is organized into fiber-like structures according to confocal microscopy of fixed slices which may guide the migration of neural precursor cells [Baier, C., S.L. Baader, J. Jankowski, V. Gieselmann, K. Schilling, U. Rauch, and J. Kappler. 2007. Hyaluronan is organized into fiber-like structures along migratory pathways in the developing mouse cerebellum. Matrix Biol. 26: 348-58]. By using plasmon surface resonance, microinjection into brain slices and fluorescence correlation spectroscopy, we show that the brain-specific lecticans bind to, but also dissociate rather rapidly from hyaluronan. After microinjection into native cerebellar slices a GFP-tagged hyaluronan-binding neurocan fragment was enriched at binding sites in the prospective white matter, which had a directional orientation and formed local stationary concentration gradients in areas where binding sites are abundant. Fluorescence correlation spectroscopy measurements at fixed brain slices revealed that fiber-bound neurocan-GFP was mobile with D(fiber(neurocan-GFP))=4x10(-10)cm(2)/s. Therefore, we propose that hyaluronan-rich fibers in the prospective white matter of the developing mouse cerebellum can guide the diffusion of lecticans. Since lecticans bind a variety of growth and mobility factors, their guided diffusion may contribute to the transport of these polypeptides and to the formation of concentration gradients. This mechanism could serve to encode positional information during development.
Kappler
Joachim
J
Institut für Biochemie und Molekularbiologie, Nussallee 11, Rheinische Friedrich-Wilhelms-Universität Bonn, 53115 Bonn, Germany. kappler@ibmb.uni-bonn.de
Hegener
Oliver
O
Baader
Stephan L
SL
Franken
Sebastian
S
Gieselmann
Volkmar
V
Häberlein
Hanns
H
Rauch
Uwe
U
D000818:Animals; D058581:Brevican; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058580:Neurocan; D011485:Protein Binding; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020349:Surface Plasmon Resonance
C553057:Bcan protein, mouse; D058581:Brevican; D011508:Chondroitin Sulfate Proteoglycans; D006025:Glycosaminoglycans; D018960:Hyaluronan Receptors; D037102:Lectins; D037181:Lectins, C-Type; C507576:Ncan protein, mouse; D009419:Nerve Tissue Proteins; D058580:Neurocan; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D006820:Hyaluronic Acid