Perlecan Antagonizes Collagen IV and ADAMTS9/GON-1 in Restricting Growth of presynaptic Boutons

Aug 22, 2014     Email"> PrintText Size

Synapses are specialized intercellular junctions between neurons where signals are propagated from one cell to another cell. Therefore, the precise formation and maintenance of an intricate synaptic network is critical for proper nervous system function. In an adult brain, most synapses tend to be retained locally within a rather confined position. Injury, behavioral enrichment, or prolonged sensory stimulation somehow can lift the growth inhibition of adult synaptogenesis. Currently, detailed knowledge of the molecular program that restricts profuse synapse growth remains elusive due to the complexity of the mammalian central nerve system.

In C. elegans, muscle cells have long neuron-like processes that run to the nerve bundles in which motor axons reside and synapses occur en passant between nerve processes and muscle arms, which is highly similar to the formation of en passant synapses in vertebrates. Recently, through genetic analysis, scientists in Dr. DING Mei’s group from the Institute of Genetics and Development Biology of the Chinese Academy of Sciences, identified that collagen type IV, collagen type XVIII and ADAMTS/GON-1 are essential for restricting en passant synapses growth.

They found that, without these molecules, ectopic synapses emerge progressively into non-synaptic regions. Perlecan/UNC-52 promotes ectopic synapse formation and functions antagonistically to collagen type IV and GON-1 but not to collagen XVIII. Thus, their results provided an important link between BM and en passant synapse growth and revealed the antagonistic role of perlecan on selective BM components during nervous system development.

In general, their study provided hints for the further related investigations in vertebrate central nerve system and shed light on the underlying mechanisms of synapse hemostasis in vivo.

This work with Dr. QIN Jianzhen as the first author has been published on the Journal of Neuroscience (2014, 34(31):10311-10324). This research was supported by the National Natural Science Foundation of China, grants from the National Basic Research Program of China, and Chinese Academy of Sciences.