The Na+/H+ exchanger NHE1 localizes as clusters to cryptic lamellipodia and accelerates collective epithelial cell migration

Helene H. Jensen; Gitte A. Pedersen; Jeanette Jeppesen Morgen; Maddy Parsons; Stine F. Pedersen; Lene N. Nejsum

doi:10.1113/jp277383

The Na⁺/H⁺ exchanger NHE1 localizes as clusters to cryptic lamellipodia and accelerates collective epithelial cell migration

Helene H. Jensen, Gitte A. Pedersen, Jeanette Jeppesen Morgen, Maddy Parsons, Stine F. Pedersen, Lene N. Nejsum^*

^*Corresponding author af dette arbejde

Cellebiologi og Fysiologi

11 Citationer (Scopus)

Abstract

Key points: Exogenous Na⁺/H⁺ exchanger 1 (NHE1) expression stimulated the collective migration of epithelial cell sheets Stimulation with epidermal growth factor, a key morphogen, primarily increased migration of the front row of cells, whereas NHE1 increased that of submarginal cell rows, and the two stimuli were additive Accordingly, NHE1 localized not only to the leading edges of leader cells, but also in cryptic lamellipodia in submarginal cell rows NHE1 expression disrupted the morphology of epithelial cell sheets and three-dimensional cysts. Abstract: Collective cell migration plays essential roles in embryonic development, in normal epithelial repair processes, and in many diseases including cancer. The Na⁺/H⁺ exchanger 1 (NHE1, SLC9A1) is an important regulator of motility in many cells and has been widely studied for its roles in cancer, although its possible role in collective migration of normal epithelial cells has remained unresolved. In the present study, we show that NHE1 expression in MDCK-II kidney epithelial cells accelerated collective cell migration. NHE1 localized to the leading edges of leader cells, as well as to cryptic lamellipodia in submarginal cell rows. Epidermal growth factor, a kidney morphogen, increased displacement of the front row of collectively migrating cells and reduced the number of migration fingers. NHE1 expression increased the number of migration fingers and increased displacement of submarginal cell rows, resulting in additive effects of NHE1 and epidermal growth factor. Finally, NHE1 expression resulted in disorganized development of MDCK-II cell cysts. Thus, NHE1 contributes to collective migration and epithelial morphogenesis, suggesting roles for the transporter in embryonic and early postnatal development.

Originalsprog	Engelsk
Tidsskrift	Journal of Physiology
Vol/bind	597
Udgave nummer	3
Sider (fra-til)	849-867
ISSN	0022-3751
DOI	https://doi.org/10.1113/jp277383
Status	Udgivet - 1 feb. 2019

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@article{e2d4fb584fc74d2e8579065ddffabfcf,

title = "The Na+/H+ exchanger NHE1 localizes as clusters to cryptic lamellipodia and accelerates collective epithelial cell migration",

abstract = "Key points: Exogenous Na+/H+ exchanger 1 (NHE1) expression stimulated the collective migration of epithelial cell sheets Stimulation with epidermal growth factor, a key morphogen, primarily increased migration of the front row of cells, whereas NHE1 increased that of submarginal cell rows, and the two stimuli were additive Accordingly, NHE1 localized not only to the leading edges of leader cells, but also in cryptic lamellipodia in submarginal cell rows NHE1 expression disrupted the morphology of epithelial cell sheets and three-dimensional cysts. Abstract: Collective cell migration plays essential roles in embryonic development, in normal epithelial repair processes, and in many diseases including cancer. The Na+/H+ exchanger 1 (NHE1, SLC9A1) is an important regulator of motility in many cells and has been widely studied for its roles in cancer, although its possible role in collective migration of normal epithelial cells has remained unresolved. In the present study, we show that NHE1 expression in MDCK-II kidney epithelial cells accelerated collective cell migration. NHE1 localized to the leading edges of leader cells, as well as to cryptic lamellipodia in submarginal cell rows. Epidermal growth factor, a kidney morphogen, increased displacement of the front row of collectively migrating cells and reduced the number of migration fingers. NHE1 expression increased the number of migration fingers and increased displacement of submarginal cell rows, resulting in additive effects of NHE1 and epidermal growth factor. Finally, NHE1 expression resulted in disorganized development of MDCK-II cell cysts. Thus, NHE1 contributes to collective migration and epithelial morphogenesis, suggesting roles for the transporter in embryonic and early postnatal development.",

keywords = "collective cell migration, EGF, MDCK cells, metastasis, Na/H exchanger, NHE1",

author = "Jensen, {Helene H.} and Pedersen, {Gitte A.} and Morgen, {Jeanette Jeppesen} and Maddy Parsons and Pedersen, {Stine F.} and Nejsum, {Lene N.}",

year = "2019",

month = feb,

day = "1",

doi = "10.1113/jp277383",

language = "English",

volume = "597",

pages = "849--867",

journal = "Journal of Physiology",

issn = "0022-3751",

publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - The Na+/H+ exchanger NHE1 localizes as clusters to cryptic lamellipodia and accelerates collective epithelial cell migration

AU - Jensen, Helene H.

AU - Pedersen, Gitte A.

AU - Morgen, Jeanette Jeppesen

AU - Parsons, Maddy

AU - Pedersen, Stine F.

AU - Nejsum, Lene N.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Key points: Exogenous Na+/H+ exchanger 1 (NHE1) expression stimulated the collective migration of epithelial cell sheets Stimulation with epidermal growth factor, a key morphogen, primarily increased migration of the front row of cells, whereas NHE1 increased that of submarginal cell rows, and the two stimuli were additive Accordingly, NHE1 localized not only to the leading edges of leader cells, but also in cryptic lamellipodia in submarginal cell rows NHE1 expression disrupted the morphology of epithelial cell sheets and three-dimensional cysts. Abstract: Collective cell migration plays essential roles in embryonic development, in normal epithelial repair processes, and in many diseases including cancer. The Na+/H+ exchanger 1 (NHE1, SLC9A1) is an important regulator of motility in many cells and has been widely studied for its roles in cancer, although its possible role in collective migration of normal epithelial cells has remained unresolved. In the present study, we show that NHE1 expression in MDCK-II kidney epithelial cells accelerated collective cell migration. NHE1 localized to the leading edges of leader cells, as well as to cryptic lamellipodia in submarginal cell rows. Epidermal growth factor, a kidney morphogen, increased displacement of the front row of collectively migrating cells and reduced the number of migration fingers. NHE1 expression increased the number of migration fingers and increased displacement of submarginal cell rows, resulting in additive effects of NHE1 and epidermal growth factor. Finally, NHE1 expression resulted in disorganized development of MDCK-II cell cysts. Thus, NHE1 contributes to collective migration and epithelial morphogenesis, suggesting roles for the transporter in embryonic and early postnatal development.

AB - Key points: Exogenous Na+/H+ exchanger 1 (NHE1) expression stimulated the collective migration of epithelial cell sheets Stimulation with epidermal growth factor, a key morphogen, primarily increased migration of the front row of cells, whereas NHE1 increased that of submarginal cell rows, and the two stimuli were additive Accordingly, NHE1 localized not only to the leading edges of leader cells, but also in cryptic lamellipodia in submarginal cell rows NHE1 expression disrupted the morphology of epithelial cell sheets and three-dimensional cysts. Abstract: Collective cell migration plays essential roles in embryonic development, in normal epithelial repair processes, and in many diseases including cancer. The Na+/H+ exchanger 1 (NHE1, SLC9A1) is an important regulator of motility in many cells and has been widely studied for its roles in cancer, although its possible role in collective migration of normal epithelial cells has remained unresolved. In the present study, we show that NHE1 expression in MDCK-II kidney epithelial cells accelerated collective cell migration. NHE1 localized to the leading edges of leader cells, as well as to cryptic lamellipodia in submarginal cell rows. Epidermal growth factor, a kidney morphogen, increased displacement of the front row of collectively migrating cells and reduced the number of migration fingers. NHE1 expression increased the number of migration fingers and increased displacement of submarginal cell rows, resulting in additive effects of NHE1 and epidermal growth factor. Finally, NHE1 expression resulted in disorganized development of MDCK-II cell cysts. Thus, NHE1 contributes to collective migration and epithelial morphogenesis, suggesting roles for the transporter in embryonic and early postnatal development.

KW - collective cell migration

KW - EGF

KW - MDCK cells

KW - metastasis

KW - Na/H exchanger

KW - NHE1

U2 - 10.1113/jp277383

DO - 10.1113/jp277383

M3 - Journal article

C2 - 30471113

AN - SCOPUS:85058654730

SN - 0022-3751

VL - 597

SP - 849

EP - 867

JO - Journal of Physiology

JF - Journal of Physiology

IS - 3

ER -