| RRC ID |
84396
|
| Author |
Kondo N, Mimori-Kiyosue Y, Tokuhiro K, Pezzotti G, Kinashi T.
|
| Title |
The autophagy component LC3 regulates lymphocyte adhesion via LFA1 transport in response to outside-in signaling.
|
| Journal |
Nat Commun
|
| Abstract |
The leukocyte integrin LFA1 is indispensable for immune responses, orchestrating lymphocyte trafficking and adhesion. While LFA1 activation induces LFA1 clustering at the cell contact surface via outside-in signaling, the regulatory mechanisms remain unclear. Here, we uncovered a previously hidden function of the autophagosome component LC3 beyond its role in autophagy by bridging two seemingly unrelated pathways: LFA1 transport and autophagosome transport. LFA1 clusters co-trafficked with LC3, facilitating LFA1 accumulation at the contact surface. LC3b knockout decreased lymphocyte adhesiveness. LFA1 activation did not induce autophagy, whereas it increased mTOR and AMPK activity. LFA1-dependent AMPK activation enhances LFA1 and LC3 clustering and adhesion. Inhibiting Mst1 kinase-mediated LC3 phosphorylation promoted LC3-mediated LFA1 recruitment to the contact surface through direct interaction with RAPL, uncovering an unprecedented integrin recruitment route. These findings uncover a function of LC3 and expand our understanding of lymphocyte regulation via LFA1.
|
| Volume |
16(1)
|
| Pages |
1343
|
| Published |
2025-2-4
|
| DOI |
10.1038/s41467-025-56631-1
|
| PII |
10.1038/s41467-025-56631-1
|
| PMID |
39905041
|
| PMC |
PMC11794545
|
| MeSH |
AMP-Activated Protein Kinases / metabolism
Animals
Autophagy*
Cell Adhesion
Humans
Lymphocyte Function-Associated Antigen-1* / genetics
Lymphocyte Function-Associated Antigen-1* / metabolism
Lymphocytes* / cytology
Lymphocytes* / metabolism
Mice
Microtubule-Associated Proteins* / genetics
Microtubule-Associated Proteins* / metabolism
Phosphorylation
Protein Transport
Signal Transduction
TOR Serine-Threonine Kinases / metabolism
|
| IF |
12.121
|
| Resource |
| Human and Animal Cells |
Ba/F3(RCB4476) |
