Abstract
Maintaining the correct ratio of apical, basal, and lateral membrane domains is important for epithelial physiology. Here, we show that CD2AP is a critical determinant of epithelial membrane proportions. Depletion of CD2AP or phosphoinositide 3-kinase (PI3K) inhibition results in loss of F-actin and expansion of apical-basal domains, which comes at the expense of lateral membrane height in MDCK cells. We demonstrate that the SH3 domains of CD2AP bind to PI3K and are necessary for PI3K activity along lateral membranes and constraining cell area. Tethering the SH3 domains of CD2AP or p110γ to the membrane is sufficient to rescue CD2AP-knockdown phenotypes. CD2AP and PI3K are both upstream and downstream of actin polymerization. Since CD2AP binds to both actin filaments and PI3K, CD2AP might bridge actin assembly to PI3K activation to form a positive feedback loop to support lateral membrane extension. Our results provide insight into the squamous to cuboidal to columnar epithelial transitions seen in complex epithelial tissues in vivo.
| Original language | English (US) |
|---|---|
| Journal | The Journal of cell biology |
| Volume | 219 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 6 2020 |
Fingerprint
ASJC Scopus subject areas
- Cell Biology
Cite this
CD2AP links actin to PI3 kinase activity to extend epithelial cell height and constrain cell area. / Wang, Yuou; Brieher, William M.
In: The Journal of cell biology, Vol. 219, No. 1, 06.01.2020.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD2AP links actin to PI3 kinase activity to extend epithelial cell height and constrain cell area
AU - Wang, Yuou
AU - Brieher, William M.
PY - 2020/1/6
Y1 - 2020/1/6
N2 - Maintaining the correct ratio of apical, basal, and lateral membrane domains is important for epithelial physiology. Here, we show that CD2AP is a critical determinant of epithelial membrane proportions. Depletion of CD2AP or phosphoinositide 3-kinase (PI3K) inhibition results in loss of F-actin and expansion of apical-basal domains, which comes at the expense of lateral membrane height in MDCK cells. We demonstrate that the SH3 domains of CD2AP bind to PI3K and are necessary for PI3K activity along lateral membranes and constraining cell area. Tethering the SH3 domains of CD2AP or p110γ to the membrane is sufficient to rescue CD2AP-knockdown phenotypes. CD2AP and PI3K are both upstream and downstream of actin polymerization. Since CD2AP binds to both actin filaments and PI3K, CD2AP might bridge actin assembly to PI3K activation to form a positive feedback loop to support lateral membrane extension. Our results provide insight into the squamous to cuboidal to columnar epithelial transitions seen in complex epithelial tissues in vivo.
AB - Maintaining the correct ratio of apical, basal, and lateral membrane domains is important for epithelial physiology. Here, we show that CD2AP is a critical determinant of epithelial membrane proportions. Depletion of CD2AP or phosphoinositide 3-kinase (PI3K) inhibition results in loss of F-actin and expansion of apical-basal domains, which comes at the expense of lateral membrane height in MDCK cells. We demonstrate that the SH3 domains of CD2AP bind to PI3K and are necessary for PI3K activity along lateral membranes and constraining cell area. Tethering the SH3 domains of CD2AP or p110γ to the membrane is sufficient to rescue CD2AP-knockdown phenotypes. CD2AP and PI3K are both upstream and downstream of actin polymerization. Since CD2AP binds to both actin filaments and PI3K, CD2AP might bridge actin assembly to PI3K activation to form a positive feedback loop to support lateral membrane extension. Our results provide insight into the squamous to cuboidal to columnar epithelial transitions seen in complex epithelial tissues in vivo.
UR - http://www.scopus.com/inward/record.url?scp=85076325430&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076325430&partnerID=8YFLogxK
U2 - 10.1083/jcb.201812087
DO - 10.1083/jcb.201812087
M3 - Article
C2 - 31723006
AN - SCOPUS:85076325430
VL - 219
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 1
ER -