TY - JOUR
T1 - Interplay of membrane crosslinking and curvature induction by annexins
AU - Mularski, Anna
AU - Sønder, Stine Lauritzen
AU - Heitmann, Anne Sofie Busk
AU - Pandey, Mayank Prakash
AU - Khandelia, Himanshu
AU - Nylandsted, Jesper
AU - Simonsen, Adam Cohen
N1 - Funding Information:
The authors acknowledge financial support from the Novo Nordisk Foundation, grant no: NNF18OC0034936.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Efficient plasma membrane repair (PMR) is required to repair damage sustained in the cellular life cycle. The annexin family of proteins, involved in PMR, are activated by Ca2+ influx from extracellular media at the site of injury. Mechanistic studies of the annexins have been overwhelmingly performed using a single annexin, despite the recruitment of multiple annexins to membrane damage sites in living cells. Hence, we investigate the effect of the presence of the crosslinking annexins, annexin A1, A2 and A6 (ANXA1, ANXA2 and ANXA6) on the membrane curvature induction of annexin A4 (ANXA4) in model membrane systems. Our data support a mechanistic model of PMR where ANXA4 induced membrane curvature and ANXA6 crosslinking promotes wound closure. The model now can be expanded to include ANXA1 and ANXA2 as specialist free edge membrane crosslinkers that act in concert with ANXA4 induced curvature and ANXA6 crosslinking.
AB - Efficient plasma membrane repair (PMR) is required to repair damage sustained in the cellular life cycle. The annexin family of proteins, involved in PMR, are activated by Ca2+ influx from extracellular media at the site of injury. Mechanistic studies of the annexins have been overwhelmingly performed using a single annexin, despite the recruitment of multiple annexins to membrane damage sites in living cells. Hence, we investigate the effect of the presence of the crosslinking annexins, annexin A1, A2 and A6 (ANXA1, ANXA2 and ANXA6) on the membrane curvature induction of annexin A4 (ANXA4) in model membrane systems. Our data support a mechanistic model of PMR where ANXA4 induced membrane curvature and ANXA6 crosslinking promotes wound closure. The model now can be expanded to include ANXA1 and ANXA2 as specialist free edge membrane crosslinkers that act in concert with ANXA4 induced curvature and ANXA6 crosslinking.
KW - Annexin A1/metabolism
KW - Annexin A4/metabolism
KW - Annexins/metabolism
KW - Cell Membrane/metabolism
KW - Models, Biological
KW - Wound Healing
U2 - 10.1038/s41598-022-26633-w
DO - 10.1038/s41598-022-26633-w
M3 - Journal article
C2 - 36581673
AN - SCOPUS:85145147064
VL - 12
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 22568
ER -