Cortactin in Lung Cell Function and Disease

Abstract

Cortactin (CTTN) is an actin-binding and cytoskeletal protein that is found in abundance in the cell cortex and other peripheral structures of most cell types. It was initially described as a target for Src-mediated phosphorylation at several tyrosine sites within CTTN, and post-translational modifications at these tyrosine sites are a primary regulator of its function. CTTN participates in multiple cellular functions that require cytoskeletal rearrangement, including lamellipodia formation, cell migration, invasion, and various other processes dependent upon the cell type involved. The role of CTTN in vascular endothelial cells is particularly important for promoting barrier integrity and inhibiting vascular permeability and tissue edema. To mediate its functional effects, CTTN undergoes multiple post-translational modifications and interacts with numerous other proteins to alter cytoskeletal structures and signaling mechanisms. In the present review, we briefly describe CTTN structure, post-translational modifications, and protein binding partners and then focus on its role in regulating cellular processes and well-established functional mechanisms, primarily in vascular endothelial cells and disease models. We then provide insights into how CTTN function affects the pathophysiology of multiple lung disorders, including acute lung injury syndromes, COPD, and asthma.

Keywords: ARDS; COPD; actin cytoskeleton; asthma; cortactin; endothelium.

Figure 1

In vitro analyses showing interaction of cortactin with MLCK in lung endothelial cells. Serum starved HPAECs were incubated with either control vehicle or HGF for 5 min, and then the association of MLCK and CTTN was detected using in situ proximity ligation assay (red dots). Representative images are shown.

Figure 2

Cortactin post-translational modifications (PTMs) participating in endothelial cell pathophysiologic responses.

Figure 3

Scheme illustrating major lung pathologies mediated by cortactin.