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First published online 14 November 2002
doi: 10.1242/jcs.00186
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Research Article |
1 Departments of Cell Biology and Histology, Sackler School of Medicine, Tel
Aviv University, Tel Aviv, 69978, Israel
2 Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel
Aviv, 69978, Israel
* Present address: Laboratory of Molecular Immunology, NHLBI, National
Institutes of Health, Bethesda, MD, USA
Author for correspondence (e-mail:
histol3{at}post.tau.ac.il)
Accepted 24 September 2002
Early endosomes and a perinuclear, Rab-11-positive compartment have been implicated in the recycling of internalized receptors. In this study, we show that synaptotagmin III (Syt III), a member of the Syt family of proteins, is required for the formation and delivery of cargo to the perinuclear endocytic recycling compartment (ERC). We demonstrate that rat basophilic leukemia (RBL-2H3) mast cells endogenously express Syt III, and >70% of this protein colocalizes with early endosomal markers, such as EEA1, annexin II and syntaxin 7, and the remaining protein colocalizes with secretory granule (SG) markers such as ß-hexosaminidase, histamine and serotonin. To study the functional role of Syt III, we stably transfected RBL cells with Syt III antisense cDNA and monitored the route of transferrin (Tfn) internalization in cells that displayed substantially reduced (<90%) levels of Syt III (RBL-Syt III-). In these cells, Tfn binding and internalization into early endosomes were unaltered. However, whereas in the mock-transfected cells Tfn was subsequently delivered to the ERC, in the RBL-Syt III- cells, Tfn remained associated with dispersed peripheral vesicles and Rab 11 remained cytosolic. Nevertheless, the rates of Tfn internalization and recycling were not affected. RBL-Syt III- cells also displayed enlarged SGs, reminiscent of the SGs present in Chediak-Higashi (beige) mice. However, morphometric analyses suggested that granule formation was unaltered and that the calculated unit granule volume is the same in both cell lines. Therefore, our results implicate Syt III as a critical factor for the generation and delivery of internalized cargo to the perinuclear endocytic recycling compartment and suggest a possible link between ERC and recycling from immature SGs during the process of SG maturation.
Key words: Endocytic recycling compartment, Endocytosis, Synaptotagmin, Transferrin, RBL-2H3 mast cells
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