Faculty Opinions recommendation of Cell adhesion molecules regulate Ca2+-mediated steering of growth cones via cyclic AMP and ryanodine receptor type 3.

Author(s):  
Vance Lemmon
2005 ◽  
Vol 170 (7) ◽  
pp. 1159-1167 ◽  
Author(s):  
Noriko Ooashi ◽  
Akira Futatsugi ◽  
Fumie Yoshihara ◽  
Katsuhiko Mikoshiba ◽  
Hiroyuki Kamiguchi

Axonal growth cones migrate along the correct paths during development, not only directed by guidance cues but also contacted by local environment via cell adhesion molecules (CAMs). Asymmetric Ca2+ elevations in the growth cone cytosol induce both attractive and repulsive turning in response to the guidance cues (Zheng, J.Q. 2000. Nature. 403:89–93; Henley, J.R., K.H. Huang, D. Wang, and M.M. Poo. 2004. Neuron. 44:909–916). Here, we show that CAMs regulate the activity of ryanodine receptor type 3 (RyR3) via cAMP and protein kinase A in dorsal root ganglion neurons. The activated RyR3 mediates Ca2+-induced Ca2+ release (CICR) into the cytosol, leading to attractive turning of the growth cone. In contrast, the growth cone exhibits repulsion when Ca2+ signals are not accompanied by RyR3-mediated CICR. We also propose that the source of Ca2+ influx, rather than its amplitude or the baseline Ca2+ level, is the primary determinant of the turning direction. In this way, axon-guiding and CAM-derived signals are integrated by RyR3, which serves as a key regulator of growth cone navigation.


Development ◽  
1989 ◽  
Vol 105 (3) ◽  
pp. 505-519 ◽  
Author(s):  
P.C. Letourneau ◽  
T.A. Shattuck

Actin filaments and their interactions with cell surface molecules have key roles in tissue cell behaviour. Axonal pathfinding during embryogenesis, an especially complex cell behaviour, is based on the migration of nerve growth cones. We have used fluorescence immunocytochemistry to examine the distribution in growth cones, their filopodia and lamellipodia of several actin-associated proteins and nerve cell adhesion molecules. The leading margins of chick dorsal root ganglion nerve growth cones and their protrusions stain strongly for f-actin, filamin, alpha-actinin, myosin, tropomyosin, talin and vinculin. MAP2 is absent from DRG growth cones, and staining for spectrin fodrin extends into growth cones, but not along filopodia. Thus, organization of the leading margins of growth cones may strongly resemble the leading lamella of migrating fibroblasts. The adhesion-mediating molecules integrin, L1, N-CAM and A-CAM are all found on DRG neurites and growth cones. However, filopodia stain relatively more strongly for integrin and L1 than for A-CAM or N-CAM. In fact, the 180 X 10(3) Mr form of N-CAM may be absent from most of the length of filopodia. DRG neurones cultured in cytochalasin B display differences in immunofluorescence staining which further emphasize that these adhesion molecules interact differentially with the actin filament system of migrating growth cones. Several models for neuronal morphogenesis emphasize the importance of regulation of the expression of adhesion molecules. Our results support hypotheses that cellular distribution and transmembrane interactions are key elements in the functions of these adhesion molecules during axonal pathfinding.


1995 ◽  
Vol 130 (4) ◽  
pp. 969-976 ◽  
Author(s):  
M Bastmeyer ◽  
H Ott ◽  
C A Leppert ◽  
C A Stuermer

Axons derived from young ganglion cells in the periphery of the retinae of larval and adult goldfish are known to fasciculate with one another and their immediate forerunners, creating the typical age-related order in the retinotectal pathway. Young axons express the E587 antigen, a member of the L1 family of cell adhesion molecules. Repeated injections of Fab fragments from a polyclonal E587 antiserum (E587 Fabs) into the eye of 3.4 cm goldfish disrupted the orderly fascicle pattern of RGC axons in the retina which was preserved in controls. Instead of bundling tightly, RGC axons crossed one another, grew between fascicles and arrived at the optic disk in a broadened front. When added to RGC axons growing in vitro, E587 Fabs neutralized the preference of growth cones to elongate on lanes of E587 protein, caused defasciculation of axons which normally prefer to grow along each other when explanted on polylysine, and prevented clustering of E587 antigen at axon-axon contact sites. Monoclonal E587 antibody disturbed axonal fasciculation moderately but led to a 30% reduction in growth velocities when axons tracked other axons. Therefore we conclude that E587 antigen mediates axonal recognition, selective fasciculation and the creation of the age-related order in the fish retina.


1999 ◽  
Vol 19 (5-6) ◽  
pp. 41 ◽  
Author(s):  
Francisco Sanchez-Madrid ◽  
Roberto González-Amaro

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 476-P
Author(s):  
YUSUKE TAKEDA ◽  
KEIICHIRO MATOBA ◽  
DAIJI KAWANAMI ◽  
YOSUKE NAGAI ◽  
TOMOYO AKAMINE ◽  
...  

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