Phospholipid phosphatase related 1 (PLPPR1) increases cell adhesion through modulation of Rac1 activity

The lipid phosphatase‐like protein PLPPR1 associates with RhoGDI1 to modulate RhoA activation in response to axon growth inhibitory molecules

“…activity (Tilve et al, 2020). Herein we demonstrate that PLPPR1 associates with RhoGDI1 to attenuate RhoA and Rac1 activity thereby modulating changes in actinomyosin dynamics (Figure 6).…”

“…Exogenous expression of PLPPR1 induces the production of actin‐rich membrane protrusions in many different cell types in culture (Broggini et al., 2016; Sigal et al., 2007; Velmans et al., 2013; Yu et al., 2015), while overexpression of PLPPR5, the closest relative of PLPPR1 in this family, produced a similar phenotype (Broggini et al., 2010). Our experiments have demonstrated that PLPPR family members interact (Yu et al., 2015), and we have recently shown that PLPPR1 can modulate cell adhesion through modulation of Rac1 activity (Tilve et al., 2020). Herein we demonstrate that PLPPR1 associates with RhoGDI1 to attenuate RhoA and Rac1 activity thereby modulating changes in actinomyosin dynamics (Figure 6).…”

“…One study has shown that PLPPR1 modulates the RhoA‐ROCK‐PIP5K signaling pathway and impedes RhoA‐mediated axon collapse in neurons (Broggini et al., 2016). We have recently demonstrated that PLPPR1 influences cell adhesion by modulating Rac1 activity (Tilve et al., 2020).…”

Plasma membrane phospholipid phosphatase-related proteins as pleiotropic regulators of neuron growth and excitability

“…Interestingly, PLPPR1 appears to counteract the effect of LPA on Rho GTPase activation and downstream signaling via interactions with RhoGDI (Iweka et al, 2020). It is also likely that counteraction of growth inhibition by PLPPR1 might represent an indirect effect, since PLPPR1 overexpression increases also the cellular adhesion on inhibitory substrates such as chondroitin sulfate proteoglycans (Tilve et al, 2020). However, it should be emphasized that these results were obtained from gain-of-function experiments with PLPPR1 (i.e., overexpression in cell lines) and there is currently no evidence that PLPPR1 counteracts Rho-mediated inhibition at 10.3389/fnmol.2022.984655 the endogenous levels in primary neurons.…”

“…As such, most studies have utilized transient overexpression or stable cell lines to study PLPPR localization to the different cellular membrane systems. In Cos-7, HeLa or N1E-115 and Neuro2a neuroblastoma cell lines, overexpressed PLPPR1, PLPPR3, PLPPR4 and PLPPR5 were located at variable levels to the plasma membrane ( Bräuer et al, 2003 ; Savaskan et al, 2004 ; Sigal et al, 2007 ; van Coevorden-Hameete et al, 2015 ; Brosig et al, 2019 ; Tilve et al, 2020 ), while PLPPR2 overexpressed in HEK293 was observed mostly in intracellular compartments ( Gross et al, 2021 ; Figure 2C ). It is highly likely that the trafficking modality and spatial organization of PLPPRs at the plasma membrane imposes additional and complementary mechanisms for controlling cellular PLPPRs responses.…”