TY - JOUR
T1 - Intracellular nanovesicles mediate α5β1 integrin trafficking during cell migration
AU - Larocque, Gabrielle
AU - Moore, Daniel J.
AU - Sittewelle, Méghane
AU - Kuey, Cansu
AU - Hetmanski, Joseph H.R.
AU - La-Borde, Penelope J.
AU - Wilson, Beverley J.
AU - Clarke, Nicholas I.
AU - Caswell, Patrick T.
AU - Royle, Stephen J.
N1 - Publisher Copyright:
© 2021 Larocque et al.
PY - 2021/10/4
Y1 - 2021/10/4
N2 - Membrane traffic is an important regulator of cell migration through the endocytosis and recycling of cell surface receptors such as integrin heterodimers. Intracellular nanovesicles (INVs) are transport vesicles that are involved in multiple membrane trafficking steps, including the recycling pathway. The only known marker for INVs is tumor protein D54 (TPD54/TPD52L2), a member of the TPD52-like protein family. Overexpression of TPD52-like family proteins in cancer has been linked to poor prognosis and an aggressive metastatic phenotype, which suggests cell migration may be altered under these conditions. Here, we show that TPD54 directly binds membrane and associates with INVs via a conserved positively charged motif in its C terminus. We describe how other TPD52-like proteins are also associated with INVs, and we document the Rab GTPase complement of all INVs. Depletion of TPD52-like proteins inhibits cell migration and invasion, while their overexpression boosts motility. We show that inhibition of migration is likely due to altered recycling of α5β1 integrins in INVs.
AB - Membrane traffic is an important regulator of cell migration through the endocytosis and recycling of cell surface receptors such as integrin heterodimers. Intracellular nanovesicles (INVs) are transport vesicles that are involved in multiple membrane trafficking steps, including the recycling pathway. The only known marker for INVs is tumor protein D54 (TPD54/TPD52L2), a member of the TPD52-like protein family. Overexpression of TPD52-like family proteins in cancer has been linked to poor prognosis and an aggressive metastatic phenotype, which suggests cell migration may be altered under these conditions. Here, we show that TPD54 directly binds membrane and associates with INVs via a conserved positively charged motif in its C terminus. We describe how other TPD52-like proteins are also associated with INVs, and we document the Rab GTPase complement of all INVs. Depletion of TPD52-like proteins inhibits cell migration and invasion, while their overexpression boosts motility. We show that inhibition of migration is likely due to altered recycling of α5β1 integrins in INVs.
UR - http://www.scopus.com/inward/record.url?scp=85111977833&partnerID=8YFLogxK
U2 - 10.1083/jcb.202009028
DO - 10.1083/jcb.202009028
M3 - Article
C2 - 34287617
AN - SCOPUS:85111977833
SN - 0021-9525
VL - 220
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 10
M1 - e202009028
ER -
