Unknown

Dataset Information

0

Clathrin regulates the association of PIPKIgamma661 with the AP-2 adaptor beta2 appendage.


ABSTRACT: The AP-2 clathrin adaptor differs fundamentally from the related AP-1, AP-3, and AP-4 sorting complexes because membrane deposition does not depend directly on an Arf family GTPase. Instead phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) appears to act as the principal compartmental cue for AP-2 placement at the plasma membrane as well as for the docking of numerous other important clathrin coat components at the nascent bud site. This PtdIns(4,5)P(2) dependence makes type I phosphatidylinositol 4-phosphate 5-kinases (PIPKIs) lynchpin enzymes in the assembly of clathrin-coated structures at the cell surface. PIPKIgamma is the chief 5-kinase at nerve terminals, and here we show that the 26-amino acid, alternatively spliced C terminus of PIPKIgamma661 is an intrinsically unstructured polypeptide that binds directly to the sandwich subdomain of the AP-2 beta2 subunit appendage. An aromatic side chain-based, extended interaction motif that also includes the two bulky C-terminal residues of the short PIPKIgamma635 variant is necessary for beta2 appendage engagement. The clathrin heavy chain accesses the same contact surface on the AP-2 beta2 appendage, but because of additional clathrin binding sites located within the unstructured hinge segment of the beta2 subunit, clathrin binds the beta2 chain with a higher apparent affinity than PIPKIgamma661. A clathrin-regulated interaction with AP-2 could allow PIPKIgamma661 to be strategically positioned for regional PtdIns(4,5)P(2) generation during clathrin-coated vesicle assembly at the synapse.

SUBMITTER: Thieman JR 

PROVIDER: S-EPMC2679492 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Clathrin regulates the association of PIPKIgamma661 with the AP-2 adaptor beta2 appendage.

Thieman James R JR   Mishra Sanjay K SK   Ling Kun K   Doray Balraj B   Anderson Richard A RA   Traub Linton M LM  

The Journal of biological chemistry 20090314 20


The AP-2 clathrin adaptor differs fundamentally from the related AP-1, AP-3, and AP-4 sorting complexes because membrane deposition does not depend directly on an Arf family GTPase. Instead phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) appears to act as the principal compartmental cue for AP-2 placement at the plasma membrane as well as for the docking of numerous other important clathrin coat components at the nascent bud site. This PtdIns(4,5)P(2) dependence makes type I phosphatidyl  ...[more]

Similar Datasets

| S-EPMC2592659 | biostudies-literature
| S-EPMC2807329 | biostudies-literature
| S-EPMC3690600 | biostudies-literature
| S-EPMC3677467 | biostudies-literature
| S-EPMC2173537 | biostudies-literature
| S-EPMC6727755 | biostudies-literature
| S-EPMC4921775 | biostudies-literature
| S-EPMC3166428 | biostudies-literature
| S-EPMC3901399 | biostudies-literature
| S-EPMC1360144 | biostudies-literature