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Vol. 19, Issue 12, 5267-5278, December 2008

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Annexin A8 Regulates Late Endosome Organization and Function

Verena Goebeler^*,,, Michaela Poeter^*,, Dagmar Zeuschner^,||, Volker Gerke^*, and Ursula Rescher^*

*Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Centre, University of Muenster, 48149 Muenster, Germany; and Department of Cell Biology, Institute of Biomembranes, University Medical Centre Utrecht, 3854 CX Utrecht, The Netherlands

Submitted April 14, 2008; Revised September 26, 2008; Accepted October 2, 2008
Monitoring Editor: Jean Gruenberg

Different classes of endosomes exhibit a characteristic intracellular steady-state distribution governed by interactions with the cytoskeleton. Late endosomes, organelles of the degradative lysosomal route, seem to require associated actin filaments for proper localization and function. We show here that the F-actin and phospholipid binding protein annexin A8 is associated specifically with late endosomes. Altering intracellular annexin A8 levels drastically affected the morphology and intracellular distribution of late endosomes. Trafficking through the degradative pathway was delayed in the absence of annexin A8, resulting in attenuated ligand-induced degradation of the epidermal growth factor receptor and prolonged epidermal growth factor-induced activation of mitogen-activated protein kinase. Depletion of annexin A8 reduced the association of late endosomal membranes with actin filaments. These results indicate that the defective cargo transport through the late endocytic pathway and the imbalanced signaling of activated receptors observed in the absence of annexin A8 results from the disturbed association of late endosomal membranes with the actin network, resulting in impaired actin-based late endosome motility.

These authors contributed equally to this work.

Present addresses: Centre for Blood Research, University of British Columbia, Vancouver V6T 1Z3, BC, Canada;

^|| Max-Planck-Institute of Molecular Biomedicine, Electron Microscopy Unit, 48149 Muenster, Germany

Address correspondence to: Ursula Rescher (rescher{at}uni-muenster.de)