Formin-mediated actin polymerization promotesSalmonellainvasion

Abstract

SummarySalmonella invade host cells using Type 3 secreted effectors, which modulate host cellular targets to promote actin rearrangements at the cell surface that drive bacterial uptake. The Arp2/3 complex contributes to Salmonella invasion but is not essential, indicating other actin regulatory factors are involved. Here, we show a novel role for FHOD1, a formin family member, in Salmonella invasion. FHOD1 and Arp2/3 occupy distinct microdomains at the invasion site and control distinct aspects of membrane protrusion formation. FHOD1 is phosphorylated during infection and this modification is required for promoting bacterial uptake by host cells. ROCK II, but not ROCK I, is recruited to the invasion site and is required for FHOD1 phosphorylation and for Salmonella invasion. Together, our studies reveal an important phospho-dependent FHOD1 actin polymerization pathway in Salmonella invasion.

Septin-regulated actin dynamics promoteSalmonellainvasion of host cells

“…Control siRNA‐treated cells displayed large membrane protrusions including finger‐like projections, known as filopodia, at the leading edge of the invasion ruffles. The cell surface also appeared rough with small filopodia‐like structures, consistent with previous studies (Truong et al, ). In contrast, knockdown of SEPTIN7 resulted in invasion ruffles with few filopodia, and the cell surface appeared smooth.…”

“…Interestingly, ROCK2 has been specifically implicated in the S . Typhimurium invasion process through its role in phosphorylating and activating FHOD1, an actin nucleator that promotes filopodia production (Truong et al, ). Thus, we examined the effect of SEPTIN7 knockdown on localisation of ROCK2 to the invasion ruffle during S .…”

FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear movement

“…In constitutively active FHOD1 ΔC, the I705A mutation prevented the normal stimulation of actin cable assembly of the WT protein (Supplementary Fig. 5; also see 9, 10 ). FHOD1 I705A rescued centrosome orientation but only partially restored rearward nuclear positioning (Fig.…”

“…Consistent with the biochemistry, expression of constitutively active FHOD1 (FHOD1 ΔC) lacking the C-terminal autoinhibitory domain in cells induces formation of thick actin cables that are decorated by the formin, another property that distinguishes FHOD1 from other DRFs 7, 8 . While recent reports imply that FHOD1 is hijacked during infection by various pathogens 9, 10 and contributes to adhesion maturation 11 , cellular functions of FHOD1 remain largely unexplored.…”

Actin dynamics in host–pathogen interaction

“…This is similar in appearance to the formation of phagocytic cups or large structures mediating macropinocytosis and engages virtually the same signaling and actin assemblies [,]. More recent research has uncovered, however, that pathogens can elicit many more and much more diverse responses in cells to induce their entry, engaging additional GTPases and actin‐dependent mechanisms unrelated to those initially identified, such as Rho‐mediated contractility or SPIRE‐ and formin‐induced actin polymerization .…”