TY - JOUR
T1 - Mesenchymal Cell Invasion Requires Cooperative Regulation of Persistent Microtubule Growth by SLAIN2 and CLASP1
AU - Bouchet, Benjamin P.
AU - Noordstra, Ivar
AU - van Amersfoort, Miranda
AU - Katrukha, Eugene A.
AU - Ammon, York Christoph
AU - ter Hoeve, Natalie D.
AU - Hodgson, Louis
AU - Dogterom, Marileen
AU - Derksen, Patrick W B
AU - Akhmanova, Anna
PY - 2016/12/19
Y1 - 2016/12/19
N2 - Microtubules regulate signaling, trafficking, and cell mechanics, but the respective contribution of these functions to cell morphogenesis and migration in 3D matrices is unclear. Here, we report that the microtubule plus-end tracking protein (+TIP) SLAIN2, which suppresses catastrophes, is not required for 2D cell migration but is essential for mesenchymal cell invasion in 3D culture and in a mouse cancer model. We show that SLAIN2 inactivation does not affect Rho GTPase activity, trafficking, and focal adhesion formation. However, SLAIN2-dependent catastrophe inhibition determines microtubule resistance to compression and pseudopod elongation. Another +TIP, CLASP1, is also needed to form invasive pseudopods because it prevents catastrophes specifically at their tips. When microtubule growth persistence is reduced, inhibition of depolymerization is sufficient for pseudopod maintenance but not remodeling. We propose that catastrophe inhibition by SLAIN2 and CLASP1 supports mesenchymal cell shape in soft 3D matrices by enabling microtubules to perform a load-bearing function.
AB - Microtubules regulate signaling, trafficking, and cell mechanics, but the respective contribution of these functions to cell morphogenesis and migration in 3D matrices is unclear. Here, we report that the microtubule plus-end tracking protein (+TIP) SLAIN2, which suppresses catastrophes, is not required for 2D cell migration but is essential for mesenchymal cell invasion in 3D culture and in a mouse cancer model. We show that SLAIN2 inactivation does not affect Rho GTPase activity, trafficking, and focal adhesion formation. However, SLAIN2-dependent catastrophe inhibition determines microtubule resistance to compression and pseudopod elongation. Another +TIP, CLASP1, is also needed to form invasive pseudopods because it prevents catastrophes specifically at their tips. When microtubule growth persistence is reduced, inhibition of depolymerization is sufficient for pseudopod maintenance but not remodeling. We propose that catastrophe inhibition by SLAIN2 and CLASP1 supports mesenchymal cell shape in soft 3D matrices by enabling microtubules to perform a load-bearing function.
KW - +TIPs
KW - 3D matrix
KW - cell migration
KW - ch-TOG
KW - CLIP-170
KW - EB1
KW - modeling
KW - Rab6
KW - Rho GTPase
KW - tumor invasion
UR - http://www.scopus.com/inward/record.url?scp=85006427814&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006427814&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2016.11.009
DO - 10.1016/j.devcel.2016.11.009
M3 - Article
C2 - 27939686
AN - SCOPUS:85006427814
VL - 39
SP - 708
EP - 723
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 6
ER -