Target recognition at the tips of postsynaptic filopodia: accumulation and function of Capricious

Abstract

While much evidence suggests that postsynaptic dynamism contributes to the formation of synapses, few studies have addressed its possible role in target selection. Do postsynaptic motile structures seek specific synaptic partner cells, as does the presynaptic growth cone? Here we studied the dynamics of myopodia, postsynaptic filopodia in Drosophila muscles, and the role of Capricious (CAPS) during the process of synaptic matchmaking. CAPS is a target recognition molecule with an extracellular domain containing leucine-rich repeat sequences. It is expressed in specific subsets of embryonic/larval body wall muscles, including muscle 12 (M12). We provide evidence that implicates the tips of myopodia as loci of initial neuromuscular recognition: (1) CAPS, expressed as a GFPfusion protein in M12, accumulated at the tips of myopodia; and (2) simultaneous live imaging of presynaptic motoneurons and postsynaptic myopodia revealed that initial neuromuscular contacts occur at the tips of myopodia. The live imaging also showed that individual postsynaptic myopodia appear to be able to discriminate partner and non-partner presynaptic cells: whereas many myopodial contacts with the partner motoneurons are stabilized to form synapses, those with non-partner neurons are retracted. In caps mutants, or in double mutants lacking both CAPS and the closely related protein Tartan, we observed fewer contacts between myopodia of M12 and the presynaptic growth cones during the process of initial neuromuscular interaction. The nascent synaptic sites of M12 were also reduced. These results provide evidence for the sensing function of postsynaptic filopodia, and implicate Caps-mediated recognition at the tips of myopodia in synaptic matching.

Recognition of pre- and postsynaptic neurons via nephrin/NEPH1 homologs is a basis for the formation of theDrosophilaretinotopic map

“…Hbs might be preferentially localized at the protrusions of pLPCs that interact with R axons. The behavior of pLPCs is analogous to 3311 RESEARCH ARTICLE Hibris/Roughest in retinotopic mapping that of developing muscle cells, which extend filopodia to the axonal targeting of innervating motoneurons (Kohsaka and Nose, 2009;Ritzenthaler et al, 2000).…”

Cytoneme-Mediated Contact-Dependent Transport of the Drosophila Decapentaplegic Signaling Protein

“…Caps and its paralog Tartan (Trn) have extracellular domains containing leucine-rich repeats (LRR) and contribute partially redundant functions to the formation of compartment boundaries of the wing disc (27). caps mutants do not mediate selection of synaptic partners normally (28–31), and Caps protein localizes at filopodia tips during partner recognition and synapse stabilization (29). We observed similar types of effects on ASP cytonemes.…”

LRT, a tendon-specific leucine-rich repeat protein, promotes muscle-tendon targeting through its interaction with Robo

“…In recent years, several Drosophila LRR proteins were demonstrated to affect targeting of motor axons and of specific muscles (Kohsaka and Nose, 2009;Kurusu et al, 2008). Intriguingly, simultaneous labeling of the presynaptic and postsynaptic sites showed that, before synapse formation, muscle membrane extensions called myopodia express the LRR protein Capricious at their tips (Kohsaka and Nose, 2009). These myopodia tips interact with axonal tips in order to form a properly located synapse.…”

“…Mutants in these genes exhibit a wide range of phenotypes, depending on their tissuespecific distribution. However, they share a common function in cell-cell recognition events (Blair, 2001;Kohsaka and Nose, 2009;Krause et al, 2006;Milan et al, 2002;Milan et al, 2005;Milan et al, 2001;Sakurai et al, 2007). Two additional LRR proteins, Haf and CG8561 (Convoluted -FlyBase), expressed by muscle cells, affect motor axon recognition of specific muscles (Kurusu et al, 2008).…”