Cortactin Promotes Migration and PDGF-induced Actin Reorganization by Signaling to Rho-GTPases.

Mol Biol Cell. 2009 May 20; Lai FP, Szczodrak M, Oelkers JM, Ladwein M, Acconcia F, Benesch S, Auinger S, Faix J, Small JV, Polo S, Stradal TE, Rottner KMonitoring Editor: David G. Drubin Dynamic actin rearrangements are initiated and maintained by actin filament nucleators, including the Arp2/3-complex. This protein assembly is activated in vitro by distinct nucleation promoting factors such as WASP/Scar family proteins or cortactin, but the relative in vivo functions of each of them remain controversial. Here we report the conditional genetic disruption of murine cortactin, implicated previously in dynamic actin reorganizations driving lamellipodium protrusion and endocytosis. Unexpectedly, cortactin-deficient cells showed little changes in overall cell morphology and growth. Ultrastructural analyses and live-cell imaging studies revealed unimpaired lamellipodial architecture, Rac-induced protrusion and actin network turnover, although actin assembly rates in the lamellipodium were modestly increased. In contrast, PDGF-induced actin reorganization and Rac activation were impaired in cortactin null cells. In addition, cortactin deficiency caused reduction of Cdc42 activity, and defects in random and directed cell migration. Reduced migration of cortactin null cells could be restored, at least in part, by active Rac and Cdc42 variants. Finally, cortactin removal did not affect the efficiency of receptor-mediated endocytosis. Together, we conclude that cortactin is fully dispensible for Arp2/3-complex activation during lamellipodia protrusion or clathrin pit endocytosis. Furthermore, we propose that cortactin promotes cell migration indirectly, through contributing to activation of selected Rho-GTPases.

Cesarean scar ectopic pregnancy in a patient with multiple prior cesarean sections: a case report.

J Reprod Med. 2009 Apr; 54(4): 251-4Kiley J, Shulman LPBACKGROUND: Cesarean scar pregnancy, an abnormal gestation implanted in the hysterotomy site of a previous cesarean section, is a unique type of ectopic pregnancy. Once uncommon, these life-threatening gestations are increasing in frequency. Outcomes depend on a high index of suspicion and early diagnosis. CASE: A 39-year-old, gravida 9, para 5-0-3-5, with a history of 5 cesarean deliveries, presented with vaginal bleeding secondary to cesarean scar pregnancy at 8 weeks' gestation. The patient, who desired future fertillty, was successfully treated conservatively with methotrexate and uterine artery embolization. CONCLUSION: Reports of cesarean scar pregnancies are rising in the literature, and we describe a scar pregnancy in a woman with multiple prior cesareans. Although the relationship between cesarean scar pregnancy and the number of previous cesarean deliveries is unclear, rising cesarean section rates worldwide will further increase overall incidence. The optimal treatment modality remains uncertain, but conservative management is appropriate when desired by the patient and administered under close observation.