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**Endocytosis and Exocytosis in Signal** 

**Transduction and in Cell Migration** 

Guido Serini1,2, Sara Sigismund3 and Letizia Lanzetti2,4

*31IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan* 

Endocytosis is a complex process that is used by eukaryotic cells to internalize fragments of plasma membrane, cell-surface receptors, and various soluble molecules. Many different mechanisms have been developed to achieve internalization of membrane-bound receptors and their ligands and they can be distinguished in clathrin-mediated endocytosis and nonclathrin internalization routes. In the clathrin-mediated endocytosis, receptors bind to the adaptor protein AP2 that, in turn, recruits clathrin to coat the invaginating pits at the plasma membrane. Coated pits are pinched off by the large GTPase dynamin to generate vesicles that traffic from the plasma membrane, undergo uncoating and fuse to the early endosomal compartment. Of note, dynamin is also required in non-clathrin-mediated endocytosis [for detailed recent reviews see (Doherty & McMahon, 2009; Loerke et al, 2009; Mettlen et al,

From early endosomes vesicles can be re-delivered to the plasma membrane through the exocytic pathway (Grant & Donaldson, 2009). Vesicle budding, uncoating, motility and fusion are controlled by the large family of Rab small GTPases. Rab proteins, in their active GTP-bound form, recruit downstream effectors that, in turn, are responsible for distinct aspects of endosomes function from signal transduction to selection and transport of cargoes. Furthermore, they control vesicular movements on microtubules thus supporting polarized distribution of internalized receptors and signalling molecules [reviewed in (Stenmark, 2009; Zerial & McBride, 2001)]. In this regards, the endo-exocytic processes are profoundly linked with the ability of the cell to elicit receptor-mediated

Endocytosis has long been considered as an attenuator of signaling as it downregulates receptors at the plasma membrane. However, the ability of internalized receptors to signal from the endosomal compartment and to be recycled to specific regions of the plasma membrane allows signal modulation both in time and in space. Indeed, endocytosismediated recycling of receptors is also a major mechanism in the execution of spatially restricted functions, such as cell motility. Moreover, the endo-exocytic cycle of adhesive receptors back and forth from the plasma membrane represents another crucial regulatory

**1. Introduction** 

2009; Traub, 2009)].

signaling cascades.

*1Cell Adhesion Dynamics Laboratory-IRCC, Candiolo 2Department of Oncological Sciences University of Torino* 

*4Membrane Trafficking Laboratory- IRCC, Candiolo* 

*Italy* 

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