Palmitoylation of Pulmonary Surfactant Protein SP-C Is Critical for Its Functional Cooperation with SP-B to Sustain Compression/Expansion Dynamics in Cholesterol-Containing Surfactant Films

Baumgart, Florian; Ospina, Olga L.; Mingarro, Ismael; Rodrı́guez-Crespo, Ignacio; Pérez‐Gil, Jesús

doi:10.1016/j.bpj.2010.08.070

Cited by 37 publications

(53 citation statements)

References 33 publications

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“…Palmitoylation is thought to be one of the main features associated with the functional activity of surfactant protein SP-C [8,11], contributing to define the optimal conditions for the re-spreading ability of LS during inspiration [24,25]. This has been related with the ability of the palmitoylated protein to maintain association of surfactant bilayers with the interfacial film, forming what has been called an interfacial surfactant reservoir.…”

Section: Discussionmentioning

confidence: 98%

“…Nevertheless, some studies have shown that the N-terminal segment of SP-C has an intrinsic tendency to interact with membranes even when it is non-palmitoylated [7], suggesting that palmitoylation may have other role in SP-C function than merely anchor the N-terminal segment to the membrane. Besides, SP-C palmitoylation has been found to be required to sustain the proper behavior of LS films in the presence of cholesterol [8] and it has also been suggested to be necessary for interconnecting the interfacial film with the different membranous layers constituting the LS reservoir in the hypophase [9], increasing the stability of surface-associated films during breathing. For all these reasons, palmitoylation appears as a key factor modulating the proper function of SP-C.…”

Section: Introductionmentioning

confidence: 99%

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Palmitoylation as a key factor to modulate SP-C–lipid interactions in lung surfactant membrane multilayers

Roldán

Goormaghtigh

Pérez‐Gil

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Surfactant protein C (SP-C) has been regarded as the most specific protein linked to development of mammalian lungs, and great efforts have been done to understand its structure-function relationships. Previous evidence has outlined the importance of SP-C palmitoylation to sustain the proper dynamics of lung surfactant, but the mechanism by which this posttranslational modification aids SP-C to stabilize the interfacial surfactant film along the compression-expansion breathing cycles, is still unrevealed. In this work we have compared the structure, orientation and lipid-protein interactions of a native palmitoylated SP-C with those of a non-palmitoylated recombinant SP-C (rSP-C) form in air-exposed multilayer membrane environments, by means of ATR-FTIR spectroscopy. Palmitoylation does not affect the secondary structure of the protein, which exhibits a full α-helical conformation in partly dehydrated phospholipid multilayer films. However, differences between the Amide I band of the IR spectrum of palmitoylated and non-palmitoylated proteins suggest subtle differences affecting the environment of their helical component. These differences are accompanied by differential effects on the IR bands from phospholipid phosphates, indicating that palmitoylation modulates lipid-protein interactions at the headgroup region of phospholipid layers. On the other hand, the relative dichroic absorption of polarized IR has allowed calculating that the palmitoylated protein adopts a more tilted transmembrane orientation than the non-palmitoylated SP-C, likely contributing to more compact, dehydrated and possibly stable multilayer lipid-protein films. As a whole, the behavior of multilayer films containing palmitoylated SP-C may reflect favorable structural properties for surfactant reservoirs at the air-liquid respiratory interface.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Palmitoylation as a key factor to modulate SP-C–lipid interactions in lung surfactant membrane multilayers

Roldán

Goormaghtigh

Pérez‐Gil

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…Besides, mechanisms involved in cholesterol sensing and mobilization may be evolutionary conserved to regulate cholesterol levels in surfactant. On the other hand, some studies suggest that SP-C might be involved in cholesterol regulation (Gómez-Gil et al, 2009a,b;Baumgart et al, 2010;Roldan et al, 2016Roldan et al, , 2017, which could also be linked to the role of SP-C in lung homeostasis. Therefore, the role of SP-C in cholesterol mobilization and dynamics could be tracked back to a combined effect of proteinand cholesterol-induced alterations on membrane structure.…”

Section: Sp-c and Cholesterol Relationships In The Lung Surfactant Comentioning

confidence: 99%

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Treumann

Baumjohann

2020

Front. Physiol.

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Sehlmeyer et al. SP-C/Cholesterol Relationships in Alveoli diffusion through lipid membranes is not well understood. However, it has been proposed that the interactions between cholesterol and the acyl carbon chains in phospholipids (stabilized by Van der Waals' forces) (Wennberg et al., 2012) create tightly packed arrangements that limits small molecule diffusion (Zocher et al., 2013). By decreasing trans-gauche rotation of the phospholipid acyl chains, membrane rigidity increases (Cassera et al., 2002; Molugu and Brown, 2019) leading to less free volume and free pockets which may accommodate oxygen, therefore reducing its flux (its partition and diffusion) through membranes (Zuniga-Hertz and Patel, 2019). Mammals developed sophisticated organs to optimize the uptake of oxygen during the life essential breathing cycle. From conducting airways to the second biggest surface exposed to the environment, the alveolar human surface (Ochs et al., 2004). In addition, the first membrane that oxygen encounters in the mammalian lungs is a complex mixture of lipids (mainly phosphatidylcholines (PC), such as dipalmitoylphosphatidylcholine (DPPC), up to a 90%) and proteins (10%) with a 5-10% of cholesterol (14-20% mol) (Zuo et al., 2008; Bernhard, 2016), called lung surfactant (surface active agent). Interestingly two surfaces in the human body present with abnormally higher cholesterol molar ratio, and both of them are in contact with the environment tightly regulating the uptake of oxygen. On the one hand, as previously explained, lung surfactant presents around a 14-20% mol cholesterol in its composition. On the other hand the eye lens surface contains up to 35% mol of cholesterol (Raguz et al., 2008; Mainali et al., 2013), compared to a normal cell plasma membrane with a 0.5 phospholipid to cholesterol molar ratio (van Meer et al., 2008; Widomska et al., 2017). Although the main function of lung Abbreviations: α-SMA, alpha smooth muscle actin; aaAMs, alternatively activated alveolar macrophages; ABCA1, ATP binding cassette transporter A1; ABCG1, ATP binding cassette transporter G1; ADA, adenosine-deaminase; ADP, adenosine diphosphate; AEC, alveolar epithelial cell; AE1C, alveolar epithelial type 1 cell; AE2C, alveolar epithelial type 2 cell; ALI

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“…Pulmonary developmental biology SP-B [14]. It should also be emphasized that the palmitoyl groups and adjacent amino acids have also been shown to promote binding to phosphatidylglycerol and lipopolysaccharide, the latter of which is unrelated to its surface active properties.…”

Section: Issn:2155-6121 Jat An Open Access Journal J Aller Thermentioning

confidence: 99%

Surfactant Protein-C in the Maintenance of Lung Integrity and Function

Glasser¹

2012

J Aller Ther

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Surfactant protein-C (SP-C) is a lung cell specific protein whose expression is identified from the earliest stages of mammalian lung development in a subset of developing epithelial cells and in the alveolar type II cell in the mature lung. Although SP-C gene expression is not critical and protein function is not necessary for the normal developing morphological patterning of the lung, studies of SP-C protein mutations and SP-C deficiency have revealed critical roles of SP-C in the maintenance and function of the preterm and mature lung during various forms of intrinsic or extrinsic lung injury. This review summarizes studies using in vitro experimental approaches, in vivo modeling in transgenic mice, and analysis of human disease pathogenesis. Collected data reveal an essential role for SP-C singly and in combination with other lung proteins, in maintenance of lung structure and pulmonary function of the immature and mature lung.

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Palmitoylation of Pulmonary Surfactant Protein SP-C Is Critical for Its Functional Cooperation with SP-B to Sustain Compression/Expansion Dynamics in Cholesterol-Containing Surfactant Films

Cited by 37 publications

References 33 publications

Palmitoylation as a key factor to modulate SP-C–lipid interactions in lung surfactant membrane multilayers

Palmitoylation as a key factor to modulate SP-C–lipid interactions in lung surfactant membrane multilayers

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Surfactant Protein-C in the Maintenance of Lung Integrity and Function

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