Although endocytosis was first described as the process mediating macromolecule or nutrient uptake through the plasma membrane, it is now recognised as a critical component of the cellular infrastructure involved in numerous processes, ranging from receptor signalling, proliferation and migration to polarity and stem cell regulation. To realise these varying roles, endocytosis needs to be finely regulated. Accordingly, multiple endocytic mechanisms exist that require specialised molecular machineries and an array of endocytic adaptor proteins with cell-specific functions. This review provides some examples of specialised functions of endocytic adaptors and other components of the endocytic machinery in different cell physiological processes, and how the alteration of these functions is linked to cancer. In particular, we focus on: (i) cargo selection and endocytic mechanisms linked to different adaptors; (ii) specialised functions in clathrin-mediated versus non-clathrin endocytosis; (iii) differential regulation of endocytic mechanisms by post-translational modification of endocytic proteins; (iv) cell context-dependent expression and function of endocytic proteins. As cases in point, we describe two endocytic protein families, dynamins and epsins. Finally, we discuss how dysregulation of the physiological role of these specialised endocytic proteins is exploited by cancer cells to increase cell proliferation, migration and invasion, leading to anti-apoptotic or pro-metastatic behaviours.

Specialised endocytic proteins regulate diverse internalisation mechanisms and signalling outputs in physiology and cancer / G. Giangreco, M.G. Malabarba, S. Sigismund. - In: BIOLOGY OF THE CELL. - ISSN 0248-4900. - 113:4(2021 Apr), pp. 165-182. [10.1111/boc.202000129]

Specialised endocytic proteins regulate diverse internalisation mechanisms and signalling outputs in physiology and cancer

G. Giangreco
Primo
;
M.G. Malabarba
Secondo
;
S. Sigismund
Ultimo
2021

Abstract

Although endocytosis was first described as the process mediating macromolecule or nutrient uptake through the plasma membrane, it is now recognised as a critical component of the cellular infrastructure involved in numerous processes, ranging from receptor signalling, proliferation and migration to polarity and stem cell regulation. To realise these varying roles, endocytosis needs to be finely regulated. Accordingly, multiple endocytic mechanisms exist that require specialised molecular machineries and an array of endocytic adaptor proteins with cell-specific functions. This review provides some examples of specialised functions of endocytic adaptors and other components of the endocytic machinery in different cell physiological processes, and how the alteration of these functions is linked to cancer. In particular, we focus on: (i) cargo selection and endocytic mechanisms linked to different adaptors; (ii) specialised functions in clathrin-mediated versus non-clathrin endocytosis; (iii) differential regulation of endocytic mechanisms by post-translational modification of endocytic proteins; (iv) cell context-dependent expression and function of endocytic proteins. As cases in point, we describe two endocytic protein families, dynamins and epsins. Finally, we discuss how dysregulation of the physiological role of these specialised endocytic proteins is exploited by cancer cells to increase cell proliferation, migration and invasion, leading to anti-apoptotic or pro-metastatic behaviours.
cancer; endocytosis; exocytosis; membrane transport; receptor signalling; adaptor proteins, signal transducing; adaptor proteins, vesicular transport; animals; apoptosis; cell membrane; cell movement; cell proliferation; clathrin; endocytosis; exocytosis; humans; neoplasm metastasis; protein transport; receptors, cell surface; signal transduction; neoplasms
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
   Discovering how signalling pathways coordinate intracellular organelle communication.
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2017E5L5P3_003

   PIANO DI SOSTEGNO ALLA RICERCA 2015-2017 - LINEA 2 "DOTAZIONE ANNUALE PER ATTIVITA' ISTITUZIONALE"
   UNIVERSITA' DEGLI STUDI DI MILANO
apr-2021
6-dic-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/903949
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