A novel AAK1 splice variant functions at multiple steps of the endocytic pathway

Davin M. Henderson, Sean D. Conner

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Phosphorylation is a critical step in regulating receptor transport through the endocytic pathway. AAK1 is a serine/ threonine kinase that is thought to coordinate the recruitment of AP-2 to receptors containing tyrosine-based internalization motifs by phosphorylating the μ2 subunit. Here we have identified a long form of AAK1 (AAK1L) that contains an extended C-terminus that encodes an additional clathrin-binding domain (CBD2) consisting of multiple low-affinity interaction motifs. Protein interaction studies demonstrate that AAK1L CBD2 directly binds clathrin. However, in vitro kinase assays reveal little difference between AAK1 isoforms in their basal or clathrin-stimulated kinase activity toward the AP-2 μ2 subunit. However, overexpression of AAK1L CBD2 impairs transferrin endocytosis, confirming an endocytic role for AAK1. Surprisingly, CBD2 overexpression or AAK1 depletion by RNA interference significantly impairs transferrin recycling from the early/sorting endosome. These observations suggest that AAK1 functions at multiple steps of the endosomal pathway by regulating transferrin internalization and its rapid recycling back to the plasma membrane from early/sorting endosome.

Original languageEnglish (US)
Pages (from-to)2698-2706
Number of pages9
JournalMolecular biology of the cell
Volume18
Issue number7
DOIs
StatePublished - Jul 2007

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