Different modes of state transitions determine pattern in the Phosphatidylinositide-Actin system

Abstract

BackgroundIn a motile polarized cell the actin system is differentiated to allow protrusion at the front and retraction at the tail. This differentiation is linked to the phosphoinositide pattern in the plasma membrane. In the highly motile Dictyostelium cells studied here, the front is dominated by PI3-kinases producing PI(3,4,5)tris-phosphate (PIP3), the tail by the PI3-phosphatase PTEN that hydrolyses PIP3 to PI(4,5)bis-phosphate. To study de-novo cell polarization, we first depolymerized actin and subsequently recorded the spontaneous reorganization of actin patterns in relation to PTEN.ResultsIn a transient stage of recovery from depolymerization, symmetric actin patterns alternate periodically with asymmetric ones. The switches to asymmetry coincide with the unilateral membrane-binding of PTEN. The modes of state transitions in the actin and PTEN systems differ. Transitions in the actin system propagate as waves that are initiated at single sites by the amplification of spontaneous fluctuations. In PTEN-null cells, these waves still propagate with normal speed but loose their regular periodicity. Membrane-binding of PTEN is induced at the border of a coherent PTEN-rich area in the form of expanding and regressing gradients.ConclusionsThe state transitions in actin organization and the reversible transition from cytoplasmic to membrane-bound PTEN are synchronized but their patterns differ. The transitions in actin organization are independent of PTEN, but when PTEN is present, they are coupled to periodic changes in the membrane-binding of this PIP3-degrading phosphatase. The PTEN oscillations are related to motility patterns of chemotaxing cells.

Actin and PIP3 waves in giant cells reveal the inherent length scale of an excited state

“…They propagate across the substrate-attached surface of the cell with one of their broadsides ahead with an average velocity of 0.12 mm6s 21 60.06 (6s.d.). The actin-rich border of the band corresponds to the actin waves previously studied in normal-sized cells (Gerisch et al, 2011). In the giant cells, these waves consist of a leading and a trailing segment ( Fig.…”

“…Several criteria relate the inner territory to the front and the external area to the tail region of a polarized cell. The membrane of the inner territory is distinguished not only by the enrichment in PIP3 and the lack of PTEN, but also by the activation of Ras (Gerisch et al, 2011). Correlated with differences in the membrane are differences in the structure and composition of the underlying actin networkthe inner territory of densely packed actin filaments is enriched in the Arp2/3 complex, whereas the external area consists of widemeshed actin bundles that are associated with myosin-II and the actin-bundling protein cortexillin .…”

Phase geometries of two-dimensional excitable waves govern self-organized morphodynamics of amoeboid cells

“…The wavefront is also accompanied by localization of PI3-kinase (Fig. S1B) and reduction in the level of PIP2 and its binding partner PTEN (22) (Fig. S1 A and B), indicating that initiation and propagation of PIP3 waves accompany consumption of its substrate PIP2.…”

“…S1 A and B), indicating that initiation and propagation of PIP3 waves accompany consumption of its substrate PIP2. It has been described that there are distinct wave patterns and that the cells spontaneously make a transition from one form to another (22). Exactly what characterizes these forms, how their transitions are determined, and how they are related to the ordered patterns of cell deformation (11) remain unclear.…”

“…S1A and S2A, and Movie S1A). The wavefront composed of F-actin and other components associated with the leading edge of chemotactic cells such as the Arp2/3 complex (13) and PIP3 (14) propagates through the "default" basal state enriched in molecules characteristic of the side and the rear of polarized cells such cortexillin I (16), ElmoA (21), and PTEN (22). The wavefront is also accompanied by localization of PI3-kinase (Fig.…”