Affinity requirements for control of synaptic targeting and neuronal cell survival by heterophilic IgSF cell adhesion molecules

SUMMARYNeurons in the developing brain express many different cell adhesion molecules (CAMs) on their surfaces, and CAM interactions are essential for the determination of synaptic connectivity patterns. CAM binding affinities can vary by more than 200-fold, but the significance of affinity differences among CAMs is unknown. Here we provide a systematic characterization of the in vivo consequences of altering CAM affinity. Interactions between DIP-α and its binding partners Dpr6 and Dpr10 control synaptic targeting and cell survival for Drosophila optic lobe neurons. We generated mutations that change DIP-α::Dpr10 binding affinity and introduced these into the endogenous loci. We show that cell survival and synaptic targeting have different affinity requirements, and that there is a threshold affinity required for targeting. Reducing affinity causes graded loss-of-function phenotypes, while increasing affinity rescues cells that would normally die. Affinity reduction can be compensated for by increasing gene copy number.

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S.4.01 Neuroplasticity and neuronal cell adhesion molecules

European Neuropsychopharmacology ◽

10.1016/s0924-977x(09)70132-4 ◽

2009 ◽

Vol 19 ◽

pp. S123-S125

Author(s):

E. Bock ◽

P.S. Walmod ◽

T. Secher ◽

V. Berezin

Keyword(s):

Cell Adhesion ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Neuronal Cell

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Ultrastructural localization of E-cadherin cell adhesion molecule on the cytoplasmic membrane of keratinocytes in vivo and in vitro.

Journal of Histochemistry & Cytochemistry ◽

10.1177/42.10.7930515 ◽

1994 ◽

Vol 42 (10) ◽

pp. 1333-1340 ◽

Cited By ~ 25

Author(s):

Y Horiguchi ◽

F Furukawa ◽

M Fujita ◽

S Imamura

Keyword(s):

Cell Adhesion ◽

Free Surface ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Cytoplasmic Membrane ◽

Ultrastructural Localization ◽

In Vivo Studies ◽

E Cadherin

We examined the ultrastructural localization of E (epithelial)-cadherin cell adhesion molecules by immunoperoxidase electron microscopy on the epithelium of mouse intestine, epidermis of human skin, and cultured human keratinocytes. The in vivo studies demonstrated that E-cadherin was present at the intermediate junction but not at the desmosome of the mouse intestinal single epithelium, and was found on the cytoplasmic membranes of keratinocytes with condensation in the intercellular space of the desmosomes, except for the basal surface of the basal cells. In vitro studies demonstrated that keratinocytes cultured in medium containing a low Ca2+ concentration (0.1 mM) lacked the tight connection through desmosomes, and that E-cadherin showed diffuse distribution and dot-like accumulation around the free surface of the cytoplasmic membrane. In culture medium containing a high concentration of Ca2+ (0.6 mM), keratinocytes formed desmosomal adhesion structures in which E-cadherin was accumulated. The free surface of the keratinocytes in this medium showed weaker distribution and a lesser amount of dot-like accumulation of E-cadherin than that in a low Ca2+ condition. These findings suggest that the distribution pattern of the E-cadherin cell adhesion molecules on the keratinocytes is different from that on the single epithelium of the intestine, and that E-cadherin on the cytoplasmic membrane of the keratinocytes shifts to the desmosomes under physiological conditions, participating in adhesion in association with other desmosomal cadherins.

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Cell Adhesion Molecules in Inflammation and Immunity: Relevance to Periodontal Diseases

Critical Reviews in Oral Biology & Medicine ◽

10.1177/10454411940050020301 ◽

1994 ◽

Vol 5 (2) ◽

pp. 91-123 ◽

Cited By ~ 25

Author(s):

John M. Crawford ◽

Keiko Watanabe

Keyword(s):

Cell Adhesion ◽

Immune Responses ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Current Knowledge ◽

Close Contact ◽

Periodontal Diseases ◽

Inflammatory Reactions ◽

Adhesive Interactions

Inflammatory and immune responses involve close contact between different populations of cells. These adhesive interactions mediate migration of cells to sites of inflammation and the effector functions of cells within the lesions. Recently, there has been significant progress in understanding the molecular basis of these intercellular contacts. Blocking interactions between cell adhesion molecules and their ligands has successfully suppressed inflammatory reactions in a variety of animal models in vivo. The role of the host response in periodontal disease is receiving renewed attention, but little is known of the function of cell adhesion molecules in these diseases. In this review we summarize the structure, distribution, and function of cell adhesion molecules involved in inflammatory/immune responses. The current knowledge of the distribution of cell adhesion molecules is described and the potential for modulation of cell adhesion molecule function is discussed.

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