PXD020639

PXD020639 is an original dataset announced via ProteomeXchange.

Title	The Ig-like domain of Punctin/MADD-4 is the primary determinant for interaction with the ectodomain of neuroligin NLG-1
Description	Punctin/MADD-4, a member of the ADAMTSL extracellular matrix protein family, was identified as an anterograde synaptic organizer in the nematode Caenorhabditis elegans. At GABAergic neuromuscular junctions, the short isoform MADD-4B binds the ectodomain of neuroligin NLG-1, itself a postsynaptic organizer of inhibitory synapses. To identify the molecular bases of their partnership, we generated recombinant forms of the two proteins and carried out a comprehensive biochemical and biophysical study of their interaction, complemented by an in vivo localisation study. We show that spontaneous proteolysis of MADD-4B first generates a shorter N-MADD-4B form, which comprises four thrombospondin (TSP) and one Ig-like domains and binds NLG-1. A second processing event eliminates the C-terminal Ig-like domain along with the ability of N-MADD-4B to bind NLG-1. These data identify the Ig-like domain as the primary determinant for N-MADD-4B interaction with NLG-1 in vitro. We further demonstrate in vivo that this Ig-like domain is essential for efficient recruitment of GABAA receptors at GABAergic synapses in C. elegans. The interaction of N-MADD-4B with NLG-1 is also disrupted by heparin, used as a surrogate for the extracellular matrix component, heparan sulphate, and whose high-affinity binding to the Ig-like domain may proceed from surface charge complementarity, as suggested by homology 3D modelling. These data point to N-MADD-4B processing and cell-surface proteoglycan binding as two possible mechanisms that can regulate the interaction between MADD-4B and NLG-1 at GABAergic synapses.
HostingRepository	PRIDE
AnnounceDate	2020-10-12
AnnouncementXML	Submission_2020-10-12_03:23:47.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Patrick FOURQUET
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-29 07:33:18	ID requested
⏵ 1	2020-10-12 03:23:48	announced

Platsaki S, Zhou X, Pinan-Lucarr, é B, Delauzun V, Tu H, Mansuelle P, Fourquet P, Bourne Y, Bessereau JL, Marchot P, The Ig-like domain of Punctin/MADD-4 is the primary determinant for interaction with the ectodomain of neuroligin NLG-1. J Biol Chem, 295(48):16267-16279(2020) [pubmed]

submitter keyword: ADAMTS-like, GABA receptor, Punctin/MADD-4, muscle, neuroligin, neuromuscular junction, nicotinic acetylcholine receptor, postsynaptic membrane, protein-protein interaction, synapse

Jean-Paul Borg
contact affiliation	Centre de Recherche en Cancérologie de Marseille Inserm UMR1068, CNRS UMR7258, Aix-Marseille Université UM105,Institut Paoli-Calmettes 13273 MARSEILLE FRANCE
contact email	jean-paul.borg@inserm.fr
lab head
Patrick FOURQUET
contact affiliation	INSERM UMR1068
contact email	patrick.fourquet@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020639
     1. Label: PRIDE project
     2. Name: The Ig-like domain of Punctin/MADD-4 is the primary determinant for interaction with the ectodomain of neuroligin NLG-1