Protein: Protein madd-4 (Punctin) (P90884)
Organism: Caenorhabditis elegans
Function: Component of an extracellular matrix cue that is involved in the guidance of dorsoventral midline migrations and in the specification of postsynaptic domains at neuromuscular junctions (NMJs). Acts as a ligand for the netrin receptor unc-40 and the neuroligin receptor nlg-1. Secreted by the dorsal and ventral nerve cords to attract sensory axons and muscle membrane extensions called muscle arms. In parallel with unc-6 and slt-1, involved in the netrin receptor unc-40 dependent guidance of the AVM and PVM mechanosensory axons along the dorsal-ventral axis. The unc-40 coreceptor eva-1 is enhancing the responsiveness of unc-40 to the madd-4 guidance cue to attract the muscle arm extensions and AVM mechanosensory axons towards the dorsoventral midline. Acts as a synaptic organizer and is required for the specification of inhibitory GABAergic and excitatory cholinergic identities of postsynaptic domains at neuromuscular junctions (NMJs). Required for the recruitment of unc-40 to both cholinergic and GABAergic NMJs. Promotes the clustering of ACh receptors and GABA(A) receptors at postsynaptic sites during synaptogenesis. The binding to the presynaptic adhesion protein nrx-1 and to the neuroligin nlg-1 at postsynaptic sites promotes clustering of GABAergic receptors at postsynaptic NMJs, thereby contributing to normal GABAergic synaptic transmission.
Subcellular location: Cell projection, axon {ECO:0000269|PubMed:22014523, ECO:0000269|PubMed:24896188}. Secreted {ECO:0000269|PubMed:22014523, ECO:0000269|PubMed:24896188}. Synapse {ECO:0000269|PubMed:24896188}. Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:22014523, ECO:0000269|PubMed:24896188}. Note=Isoform b is secreted by cholinergic and GABAergic motoneurons and localizes to excitatory cholinergic and inhibitory GABAergic NMJs, whereas isoform a and isoform c are exclusively secreted by cholinergic motoneurons and localize to excitatory cholinergic NMJs. {ECO:0000269|PubMed:22014523, ECO:0000269|PubMed:24896188}.
Interaction partners:
- Netrin receptor unc-40
- Adenosine 3'-phospho 5'-phosphosulfate transporter 2
- Neuroligin-1
- Netrin unc-6
- Spectrin alpha chain
- Moesin/ezrin/radixin homolog 1
- E3 ubiquitin-protein ligase TRIM9
Sequence:
MKCSYTVVFLLFYLLIASFHVDALSWAAWSPWSSCTKTCGGGVSRQLRRCLTSKCSGESVRFKVCAQKTCESKSRLARDTICGGEEIVSRGQCEVVCRSRLTGANFLWRVDDGTPCQAATSRAVCSKGSCQIVGCDGLISSSFRFDACGVCGGRGDTCDNGKFIWKVSEEYTACASNCDDIVDWSGAGRSIASTSQPIVVCVNAITGRVVPEKLCADKLRPKVEARPCPMLICPSRCRWMAADWTECVPHCGEGTRKREVYCVQTAHNVTVHVPDTFCENGTRPAAEENCVSTSCGRWEAGKWSKCTASCGQGVRRRHVACVGGSDCDEGGRPRQETTCYAGIPCSIATNSLDWNDRAYLDGNTFGSMDNHNDWQAPRLVAGEWSTCSSTCGTGVMSRTVECVAVNPISSAPIKLPMSECQDQEQPKLFESCEVRSCPLQEDSKLSEDEAPYQWRYGDWTQCSASCLGGKQKAALKCIQVSTGKSVQWSQCDARRRPPEKSRPCNQHPCPPFWLTSKYSDCSMSCGSGTARRSVKCAQTVSKTDGADAHIVLRDDRCHFKKPQETETCNVVACPATWVTAQWTECSRSCDSGERRRQVWCEIRDSRGKTQRRPDVECDANTKPQTVEVCSFGSCSRPELLSNRVFEQNAEQKKLTLGIGGVATLYQGTSIKIKCPAKKFDKKKIYWKKNGKKIKNDAHIKVSANGNLRVFHARMEDAGVYECFTDRLQGNVTLNFKYRDFPASRVDLAPKPQIPSTKNRQRVQVSKEDVLREQASVLHKMNVSLIEALLTAPNDEKAREQLRKYGNELVARWDIGHWSECRQKTCHVAGYQARGISCKVTFHGEIRNVDNSICESLASVRPPETRPCHREDCPRWEASQWSECSSQRCVSSMLAQKRRNVTCRFTNGTSVDIQHCDITNRPATTMDCPNQNCKAEWRTSDWGSCSSECGTGGVQLRLLSCVWISSGRPAGRNCEQMRRPHSARACVADEPLPPCMPTASALYQRDASCQDQSRFCDIIKLFHSCDSLEVRQKCCSTCTFVERKKF