Editing Pseudopodia (section)

==Formation==
Cells which make pseudopods are generally referred to as ''[[amoeboids]]''.<ref>{{cite encyclopedia |title=Pseudopodia |encyclopedia=[[Encyclopedia.com]] |url=https://www.encyclopedia.com/history/latin-america-and-caribbean/mesoamerican-indigenous-peoples/pseudopodia |access-date=2018-12-16}}</ref>

===Via extracellular cue===
To move towards a target, the cell uses [[chemotaxis]]. It senses extracellular signalling molecules, chemoattractants (e.g. cAMP for ''[[Dictyostelium]]'' cells),<ref name="Bosgraaf2009">{{Cite journal | author=Bosgraaf L & Van Haastert PJM | title=The Ordered Extension of Pseudopodia by Amoeboid Cells in the Absence of External Cues | journal=PLOS ONE | volume=4 |issue= 4 | year=2009 | pages=626–634 | doi=10.1371/journal.pone.0005253 | pmc=2668753 | pmid=19384419| bibcode=2009PLoSO...4.5253B | doi-access=free }}</ref> to extend pseudopodia at the membrane area facing the source of these molecules.

The chemoattractants bind to [[G&nbsp;protein-coupled receptor]]s, which activate [[Rho family of GTPases|GTPases of the Rho family]] (e.g. Cdc42, Rac) via [[G&nbsp;protein]]s.

Rho GTPases are able to activate [[Wiskott–Aldrich syndrome protein|WASp]] which in turn activate [[Arp2/3 complex]] which serve as nucleation sites for [[Actin#Nucleation and polymerization|actin polymerization]].<ref name="Haastert2004">{{Cite journal | author=Van Haastert PJM & Devreotes PN | title=Chemotaxis: signalling the way forward | journal=Nature Reviews Molecular Cell Biology | volume=5 | year=2004 | issue=8 | pages=626–634 | doi=10.1038/nrm1435 | pmid=15366706 | s2cid=5687127 }}</ref> The actin polymers then push the membrane as they grow, forming the pseudopod. The pseudopodium can then adhere to a surface via its [[Cell adhesion|adhesion proteins]] (e.g. [[integrin]]s), and then pull the cell's body forward via contraction of an actin-myosin complex in the pseudopod.<ref name="Campbell2017">{{Cite journal | author=Campbell EJ | title=A computational model of amoeboid cell swimming| journal=Physics of Fluids | volume=29 | year=2017 | issue=10| doi=10.1063/1.4990543 | page=101902| bibcode=2017PhFl...29j1902C}}</ref><ref name="Conti2008">{{Cite journal | author=Conti MA | title=Nonmuscle myosin II moves in new directions| journal=Journal of Cell Science | volume=121 | year=2008 | issue=Pt 1| pages=11–18 | doi=10.1242/jcs.007112 | pmid=18096687 | s2cid=16367236| doi-access= }}</ref> This type of locomotion is called ''[[amoeboid movement]]''.

Rho GTPases can also activate [[phosphatidylinositol 3-kinase]] (PI3K) which recruit [[Phosphatidylinositol (3,4,5)-trisphosphate|PIP<sub>3</sub>]] to the membrane at the leading edge and detach the PIP<sub>3</sub>-degrading enzyme [[PTEN (gene)|PTEN]] from the same area of the membrane. PIP<sub>3</sub> then activate GTPases back via [[Guanine nucleotide exchange factor|GEF]] stimulation. This serves as a feedback loop to amplify and maintain the presence of local GTPase at the leading edge.<ref name="Haastert2004" />

Otherwise, pseudopodia cannot grow on other sides of the membrane than the leading edge because myosin filaments prevent them to extend. These myosin filaments are induced by [[Cyclic guanosine monophosphate|cyclic GMP]] in ''[[Dictyostelium discoideum|D. discoideum]]'' or [[Rho kinase]] in [[neutrophil]]s for example.<ref name="Haastert2004" />

Different physical parameters were shown to regulate the length and time-scale of pseudopodia formation. For example, an increase in membrane [[Tension (physics)|tension]] inhibits actin assembly and protrusion formation.<ref>{{Cite journal |last1=Houk |first1=Andrew R. |last2=Jilkine |first2=Alexandra |last3=Mejean |first3=Cecile O. |last4=Boltyanskiy |first4=Rostislav |last5=Dufresne |first5=Eric R. |last6=Angenent |first6=Sigurd B. |last7=Altschuler |first7=Steven J. |last8=Wu |first8=Lani F. |last9=Weiner |first9=Orion D. |date=2012-01-20 |title=Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration |journal=Cell |volume=148 |issue=1–2 |pages=175–188 |doi=10.1016/j.cell.2011.10.050 |issn=0092-8674 |pmc=3308728 |pmid=22265410}}</ref> It was demonstrated that the lowered negative [[surface charge]] on the inner surface of the [[Cell membrane|plasma membrane]] generates protrusions via activation of the Ras-[[PI3K/AKT/mTOR pathway|PI3K/AKT/mTOR]] signalling pathway.<ref>{{Cite journal |last1=Banerjee |first1=Tatsat |last2=Biswas |first2=Debojyoti |last3=Pal |first3=Dhiman Sankar |last4=Miao |first4=Yuchuan |last5=Iglesias |first5=Pablo A. |last6=Devreotes |first6=Peter N. |date=2022-10-06 |title=Spatiotemporal dynamics of membrane surface charge regulates cell polarity and migration |journal=[[Nature Cell Biology]] |volume=24 |issue=10 |pages=1499–1515 |doi=10.1038/s41556-022-00997-7 |issn=1476-4679 |pmid=36202973|s2cid=248990694 |pmc=10029748 }}</ref>

===Without extracellular cue===
In the case there is no extracellular cue, all moving cells navigate in random directions, but they can keep the same direction for some time before turning. This feature allows cells to explore large areas for colonization or searching for a new extracellular cue.

In ''Dictyostelium'' cells, a pseudopodium can form either ''de novo'' as normal, or from an existing pseudopod, forming a Y-shaped pseudopodium.

The Y-shaped pseudopods are used by ''Dictyostelium'' to advance relatively straight forward by alternating between retraction of the left or right branch of the pseudopod. The ''de novo'' pseudopodia form at different sides than pre-existing ones, they are used by the cells to turn.

Y-shaped pseudopods are more frequent than ''de novo'' ones, which explain the preference of the cell to keep moving to the same direction. This persistence is modulated by [[Phospholipase A2|PLA2]] and cGMP signalling pathways.<ref name="Bosgraaf2009" />