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The receptor tyrosine phosphatase CRYPalpha affects growth cone morphology
B K Mueller1, M M Ledig, S Wahl
1Max-Planck-Institut für Entwicklungsbiologie, Abteilung I (Physikalische Biologie), Spemannstr. 35/I, D-72076 Tübingen, Federal Republic of Germany.
Abstract:
During development of the nervous system receptor tyrosine kinases and receptor protein tyrosine phosphatases act in a coordinate way during axon growth and guidance. In the developing avian retinotectal system, many different receptor protein tyrosine phosphatases are expressed. Most of them have unknown functions. Retinal ganglion cells express at least three different members of this receptor family on their axons and growth cones: CRYPalpha, CRYP-2 and PTPmu. CRYPalpha interacts heterophilically with at least two different ligands found in the basal membranes of the retina and the optic tectum. To analyze the role of the CRYPalpha-ligand interaction, retinal ganglion cell axons were grown on retinal basal membranes (inner limiting membrane) and the receptor-ligand interaction was blocked from both the receptor side (by receptor specific antibodies) and from the ligand side by using a receptor-alkaline phosphatase fusion protein. Both of these treatments reduced average retinal axon length and induced a dramatic change in morphology of retinal ganglion cell growth cones on basal membranes, but not on other substrates like laminin, N-cadherin, matrigel- and detergent-treated basal membranes. These results suggest that CRYPalpha and its ligand act as growth-promoting molecules during intraretinal axon growth.
Insights
CRYPalpha, a receptor tyrosine phosphatase, and its ligand promote axon growth in the developing nervous system. Blocking this interaction reduced axon length and altered growth cone morphology in retinal ganglion cells.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Receptor tyrosine kinases and phosphatases coordinate axon growth and guidance in the nervous system.
- Several receptor protein tyrosine phosphatases (RPTPs) are expressed in the avian retinotectal system, but their functions are largely unknown.
- Retinal ganglion cells express CRYPalpha, CRYP-2, and PTPmu RPTPs on their axons and growth cones.
Purpose of the Study:
- To investigate the function of the CRYPalpha-ligand interaction in intraretinal axon growth.
- To determine the role of CRYPalpha in the developing avian retinotectal system.
Main Methods:
- Retinal ganglion cell axons were grown on retinal basal membranes (inner limiting membrane).
- The CRYPalpha-ligand interaction was blocked using receptor-specific antibodies and a receptor-alkaline phosphatase fusion protein.
- Axon length and growth cone morphology were analyzed on various substrates.
Main Results:
- Blocking the CRYPalpha-ligand interaction significantly reduced retinal axon length.
- This blockage induced dramatic morphological changes in retinal ganglion cell growth cones on basal membranes.
- These effects were specific to basal membranes and not observed on substrates like laminin or N-cadherin.
Conclusions:
- CRYPalpha and its ligand function as growth-promoting molecules during intraretinal axon development.
- The CRYPalpha-ligand interaction is crucial for normal axon growth and guidance within the retina.
- This interaction plays a specific role in the context of the retinal basal membrane.