Noncentrosomal microtubules regulate autophagosome transport through CAMSAP2‐EB1 cross‐talk

Abstract

Microtubules (MTs) play essential roles in many steps of autophagy, an important degradation pathway in the maintenance of cellular homoeostasis. In many cells, MT networks are comprised of centrosomal MTs and noncentrosomal MTs. However, it is unknown whether noncentrosomal MTs and its binding proteins are involved in autophagy. Here, we show in HeLa cells that calmodulin-regulated spectrin-associated protein 2 (CAMSAP2), a noncentrosomal MT minus-end stabilizing protein, regulates retrograde transport of autophagosomes through MT dynamics. CAMSAP2 cooperates with EB1 to regulate end-binding protein 1 (EB1) behaviour at MT plus ends, MT growth directions and autophagosome transport. An association between CAMSAP2 and EB1 in the cytosol may modulate EB1 binding to MT plus ends. Collectively, our data indicate that noncentrosomal MTs regulate autophagy through a cross-talk between CAMSAP2 and EB1.

CAMSAP3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation

“…24 Recently, vimentin was shown to be transported bidirectionally along the microtubule cytoskeleton, 43 and CAMSAP family proteins regulate the trafficking of cargo through microtubule dynamics. 16 CAMSAP3 might probably interact with vimentin in this event. Proteomic analysis also indicated an interplay among CAMSAP3, ERK, and vimentin (Figure 5), suggesting that vimentin is an intermediate scaffold for CAMSAP3-regulated ERK activity.…”

“…Recently, the calmodulin-regulated spectrin-associated protein (CAMSAP) family has gained increasing attention in cancer cell biology. 16 CAMSAPs, non-centrosomal microtubule minus-end binding proteins, are required for maintaining microtubule organization and cellular morphogenesis. [16][17][18] The CAMSAP family comprises CAMSAP1, CAMSAP2, and CAMSAP3, and we reported that CAMSAP3 maintains the epithelial state of lung cancer-derived cells, preventing them from epithelialmesenchymal transition (EMT), which is a form of cell changes associated with cancer progression.…”

“…16 CAMSAPs, non-centrosomal microtubule minus-end binding proteins, are required for maintaining microtubule organization and cellular morphogenesis. [16][17][18] The CAMSAP family comprises CAMSAP1, CAMSAP2, and CAMSAP3, and we reported that CAMSAP3 maintains the epithelial state of lung cancer-derived cells, preventing them from epithelialmesenchymal transition (EMT), which is a form of cell changes associated with cancer progression. 19 Gene expression profiling data have shown that lung cancer tissues with low CAMSAP3 expression levels are closely associated with a decreasing overall survival rate of lung adenocarcinoma patients.…”

Intraflagellar transport 20 promotes collective cancer cell invasion by regulating polarized organization of Golgi‐associated microtubules

“…In this regard, it is worth noting that CAMSAP2 recognizes MT minus ends and tethers them to the cis ‐Golgi membrane to protect them from depolymerization, independent of γ‐TuRC‐mediated MT nucleation at the cis ‐Golgi . Additionally, CAMSAP2 is known to cooperate with EB1 and EB3 at the Golgi apparatus to regulate MT growth dynamics and Golgi reorientation . Our findings indicate that IFT20 is required for polarized and continuous MT growth and for Golgi reorientation during collective invasion.…”

“…is known to cooperate with EB1 and EB3 at the Golgi apparatus to regulate MT growth dynamics and Golgi reorientation. 53,54 Our findings indicate that IFT20 is required for polarized and continuous MT growth and for Golgi reorientation during collective invasion. Thus, there might be a link between IFT20 and CAMSAP2 in regulating MT dynamics at the Golgi apparatus, required for proper organization of Golgi-associated MTs and Golgi polarity during collective invasion.…”