Cell Adhesion Molecules in Synapse Formation

AbstractL1-type cell adhesion molecules (CAMs) are important mediators of neural differentiation, including axonal outgrowth and pathfinding and also of synapse formation and maintenance. In addition, their interactions with cytoskeletal components are highly conserved and regulated. How these different aspects of CAM functionality relate to each other is not well understood. Based on results from our and other laboratories we propose that ankyrin-binding to L1-type CAMs provides a master switch. The interaction with ankyrins directs L1-type adhesive proteins into different functional contexts, either ankyrin-independent functions, such as neurite outgrowth and axonal pathfinding or into ankyrin-dependent functions, such as L1’s role at axon initial segments (AIS), paranodal regions, synapses and in dendrites.

Download Full-text

In situ screening for postsynaptic cell adhesion molecules during synapse formation

The Journal of Biochemistry ◽

10.1093/jb/mvx030 ◽

2017 ◽

Author(s):

Takeshi Uemura ◽

Tomoko Shiroshima ◽

Asami Maeda ◽

Misato Yasumura ◽

Takashi Shimada ◽

...

Keyword(s):

Cell Adhesion ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Synapse Formation ◽

Postsynaptic Cell

Download Full-text

MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0517 ◽

2014 ◽

Vol 369 (1652) ◽

pp. 20130517 ◽

Cited By ~ 20

Author(s):

Cecilia S. Lu ◽

Bo Zhai ◽

Alex Mauss ◽

Matthias Landgraf ◽

Stephen Gygi ◽

...

Keyword(s):

Cell Adhesion ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Synapse Formation ◽

Neuromuscular Junctions ◽

Neuromuscular Synapse ◽

Fine Tuning ◽

Synapse Development ◽

Stable Isotope Labelling ◽

Coordinate Regulation

Neuronal connectivity and specificity rely upon precise coordinated deployment of multiple cell-surface and secreted molecules. MicroRNAs have tremendous potential for shaping neural circuitry by fine-tuning the spatio-temporal expression of key synaptic effector molecules. The highly conserved microRNA miR-8 is required during late stages of neuromuscular synapse development in Drosophila . However, its role in initial synapse formation was previously unknown. Detailed analysis of synaptogenesis in this system now reveals that miR-8 is required at the earliest stages of muscle target contact by RP3 motor axons. We find that the localization of multiple synaptic cell adhesion molecules (CAMs) is dependent on the expression of miR-8, suggesting that miR-8 regulates the initial assembly of synaptic sites. Using stable isotope labelling in vivo and comparative mass spectrometry, we find that miR-8 is required for normal expression of multiple proteins, including the CAMs Fasciclin III (FasIII) and Neuroglian (Nrg). Genetic analysis suggests that Nrg and FasIII collaborate downstream of miR-8 to promote accurate target recognition. Unlike the function of miR-8 at mature larval neuromuscular junctions, at the embryonic stage we find that miR-8 controls key effectors on both sides of the synapse. MiR-8 controls multiple stages of synapse formation through the coordinate regulation of both pre- and postsynaptic cell adhesion proteins.

Download Full-text