PXD021138

PXD021138 is an original dataset announced via ProteomeXchange.

Title	Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis
Description	Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Parallel to Clathrin-mediated endocytosis, additional Clathrin-independent endocytic routes exist, including fast Endophilin-mediated endocytosis (FEME). The latter is not constitutively active but requires the activation of selected receptors. In cell culture, however, the high levels of growth factors in the regular culture media induce spontaneous FEME, which can be suppressed upon serum starvation. Thus, we predicted a role for protein kinases in this growth factor receptor-mediated regulation of the pathway. Using chemical and genetic inhibition, we found that Cdk5 and GSK3β are negative regulators of FEME. Their inhibition was sufficient to activate FEME promptly in resting cells and boosted the production of endocytic carriers containing β 1-adrenergic receptor, following dobutamine addition. We established that the kinases suppress FEME at several levels. They control Dynamin-1 and Dynein recruitment and sorting of cargo receptors such as Plexin A1 and ROBO1 into FEME carriers. They do so by antagonizing the binding of Endophilin to Dynamin-1 as well as to Collapsin response mediator protein 4 (CRMP4), a Plexin A1 adaptor. Cdk5 and GSK3β also hamper the binding and recruitment of Dynein onto FEME carriers by Bin1. Interestingly, we found that GSK3β binds to Endophilin, thus imposing a local regulation of FEME. Collectively, these findings place the two kinases as key regulators of FEME, licensing cells for rapid uptake by the pathway only upon when Cdk5 and GSK3β activity is low.
HostingRepository	PRIDE
AnnounceDate	2021-05-28
AnnouncementXML	Submission_2021-05-28_02:20:55.749.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juliette James
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-26 04:28:27	ID requested
⏵ 1	2021-05-28 02:20:56	announced

Ferreira APA, Casamento A, Carrillo Roas S, Halff EF, Panambalana J, Subramaniam S, Sch, ü, tzenhofer K, Chan Wah Hak L, McGourty K, Thalassinos K, Kittler JT, Martinvalet D, Boucrot E, inhibit fast endophilin-mediated endocytosis. Nat Commun, 12(1):2424(2021) [pubmed]

submitter keyword: LC-MS

Emmanuel Boucrot
contact affiliation	University College London ISMB
contact email	e.boucrot@ucl.ac.uk
lab head
Juliette James
contact affiliation	UCL
contact email	zcbtjdw@ucl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021138
     1. Label: PRIDE project
     2. Name: Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis