期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 42, 期 5, 页码 580-584出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2009.12.020
关键词
Annexin A6; Endosomes; Cholesterol; Caveolin-1; EGFR/Ras inactivation
资金
- National Health and Medical Research Council of Australia [510293, 510294]
- National Heart Foundation of Australia [G06S2559]
- Ministerio de Ciencia y Tecnologia [BFU2009-10335]
- Ministerio de Sanidad y Consumo [RTICC-2006 ISCII]
- Fundacio Marato TV3 (Barcelona, Spain) [PI040236]
- Beatriu de Pinos fellowship (Generalitat de Catalunya)
Annexin A6 (AnxA6) belongs to the highly conserved annexin protein family. Like other annexins, the function of AnxA6 is linked to its ability to bind phospholipids in a Ca(2+)-dependent manner, thereby interacting with cellular membranes in a dynamic, reversible and regulated fashion. Upon cell activation, AnxA6 is recruited to the plasma membrane, endosomes and caveolae/membrane rafts to interact with signalling proteins, the endocytic machinery and actin cytoskeleton to inhibit epidermal growth factor receptor and Ras signalling. In addition, AnxA6 associates with late endosomes to regulate cholesterol export leading to reduced cytoplasmic phospholipase A2 activity and caveolae formation. Accordingly, AnxA6 may function as an organizer of membrane domains (i) to create a scaffold for the formation of multifactorial signalling complexes, (ii) to regulate transient membrane-actin interactions during endocytic transport, and (iii) to modulate intracellular cholesterol homeostasis. Altogether, this will regulate critical physiological processes including proliferation, differentiation, inflammation and cell migration. (C) 2010 Elsevier Ltd. All rights reserved.
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