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J Cell Sci. 2019 Jan 7. pii: jcs.224998. doi: 10.1242/jcs.224998. [Epub ahead of print]

Akt and SGK protein kinases are required for efficient feeding by macropinocytosis.

Author information

1
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK thomasw@mrc-lmb.cam.ac.uk.
2
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.

Abstract

Macropinocytosis is an actin-driven process of large-scale, non-specific fluid uptake used for feeding by some cancer cells and the macropinocytosis model organism Dictyostelium discoideum In Dictyostelium, macropinocytic cups are organised by 'macropinocytic patches' in the plasma membrane. These contain activated Ras, Rac and PI(3,4,5)P3 and direct actin polymerisation to their periphery. We show that an Akt (PkbA) and an SGK (PkbR1) protein kinase act downstream of PI(3,4,5)P3 and are together nearly essential for fluid uptake. This pathway enables the formation of larger macropinocytic patches and macropinosomes, thereby dramatically increasing fluid uptake. Through phosphoproteomics, we identify a RhoGAP, GacG, as a PkbA/PkbR1 target and show it is required for efficient macropinocytosis and expansion of macropinocytic patches. The function of Akt and SGK in cell feeding through control of macropinosome size has implications for cancer cell biology.

KEYWORDS:

Akt; Dictyostelium; Endocytosis; Macropinocytosis; PI3-kinase; SGK

PMID:
30617109
DOI:
10.1242/jcs.224998

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