| the WAVE regulatory complex
(WRC) |
SopB, SopE, SptP |
the WRC complex is essential
for the formation of lamellipodia, which is governed by Rac1 and Arf1
activity. GEF mimic SopE can activate Rac1, and Arf1 is activated
by activity of SopB, which helps in the accumulation of PI (3,4,5)
P3 and ARNO at the site of entry, leading to the recruitment of WRC
and the promotion of the Arp2/3 complex
for actin remodelling. SptP is responsible for the inactivation of
Rac1 and returning the cell to the resting stage. |
(267−275) |
| the
WASH complex |
not
identified |
the WASH
(Wiskott–Aldrich
syndrome protein and scar homologue) complex, also responsible for
activating Arp2/3-dependent actin polymerization,
acts downstream of RhoA and accumulates at the Salmonella entry site. |
(270, 276, 277) |
| myosin-mediated contractility |
SopB |
actin stress fibers are
decorated with myosin IIA and IIB upon infection. SopB helps in hijacking
and activating myosin II through the activation of RhoA and downstream
Rho kinases (Rocks). the exact molecular mechanism remains elusive,
but altered phosphoinositide dynamics might be involved. |
(128, 278) |
| formins |
SopB, SopE/E2 |
formins are a family of
proteins that are nucleators of actin polymerization independently
of Arp2/3. FHOD1 also lies downstream
of RhoA and can be activated by Rac1. SPIRE1 (pathogen entry) and
SPIRE2 (replicative niche) are also involved in cytoskeleton remodelling,
as these help in nucleating the assembly/bundling of straight actin
fiber. |
(130, 135, 279, 280) |
| the exocyst complex |
SipC, SopE/E2 |
Exo70 is part of a hetero-octameric
exocyst complex that helps in vesicle transport, and it interacts
with SipC. assembly of an exocyst complex requires activation of RelA
by SopE/E2. the exact molecular mechanism for this complex-mediated
entry also remains elusive, however, it is proposed that it may fulfill
the extra phospholipids requirement during the formation of membrane
ruffles. |
(281) |
| IQGAP1 |
SopE/E2, SopB |
IQGAP1 has a homologous
domain of GTPase activating protein (GAP, inactivators of Rho GTPases),
thus it binds GTPases (Rac1 and Cdc42) and prevents its inactivation.
IQGAP1 also acts as a molecular scaffold for downstream MAPK/ERK signaling
and various phosphoinositide kinases that might be in relation to
SopB. |
(282−285) |
| annexins |
SopE/E2, SopB |
annexins (A1, A2 and A5)
are calcium-dependent membrane=binding proteins that indirectly regulate
cytoskeleton membrane dynamics, and they accumulate at the site of Salmonella-mediated entry. A2 along with p11 protein binds
AHNAK (a phosphoprotein regulator of membrane). exact molecular dynamics
have yet to be elucidated. |
(286) |
| myosin
VI |
SopE/E2, SopB |
myosin VI plays a key role
in endocytosis, and SopE specifically recruits it at the site of entry
via Rac1-WRC and Rac1-p21activated kinase (PAK) pathway. myosin VI
also recruits a PI3P-binding, actin-binding and GEF for Cdc42 called
frabin at the site of membrane ruffles. |
(128, 272, 287−289) |
| villin |
SipA, SptP |
villin, an actin-binding
and severing protein, is required for Salmonella to
enter into the polarized enterocytes. it is suggested that severing
leads to the generation of barbed ends, which are essential for new
filament growth. the activity of villin is regulated by SipA and SptP. |
(290) |
