Extracellular Matrix Muscle Arm Development Defective Protein Cooperates with the One Immunoglobulin Domain Protein To Suppress Precocious Synaptic Remodeling

Synaptic remodeling plays important roles in health and neural disorders. Although previous studies revealed that several transcriptional programs control synaptic remodeling in the nematode Caenorhabditis elegans, the molecular mechanisms of the dorsal D-type (DD) synaptic remodeling are poorly understood. Here we show that extracellular matrix molecule muscle arm development defective protein-4 (MADD-4) cooperates with the one immunoglobulin domain protein-1 (OIG-1) to defer precocious DD synaptic remodeling. Specifically, loss of MADD-4 exhibited the precocious DD synaptic remodeling. The long isoform MADD-4L is dynamically expressed while the short isoform MADD-4B is persistently expressed in DD neurons of L1 stage. In the unc-30 mutant lacking the Pitx-type homeodomain transcription factor UNC-30, the expression levels of both MADD-4B and -L isoforms were dramatically downregulated in DD neurons of the L1 stage. Our further data showed that MADD-4B and -L isoforms physically interact with OIG-1 and madd-4 acts in the oig-1 genetic pathway to modulate the DD synaptic remodeling. Our findings demonstrated that the extracellular matrix plays a novel role in synaptic plasticity.

Automated summary

The study revealed that muscle arm development defective protein-4 (MADD-4) cooperates with one immunoglobulin domain protein-1 (OIG-1) to delay the occurrence of DD synaptic remodeling in nematodes, demonstrating a novel role for the extracellular matrix in synaptic plasticity. This sheds light on the molecular mechanisms involved in dorsal D-type (DD) synaptic remodeling, particularly in the role of MADD-4 in the process.