Microtubule-associated protein6 (MAP6) is a calmodulin binding protein that is involved in microtubule stabilisation []. Neurons contain abundant subsets of highly stable microtubules that resist de-polymerising conditions such as exposure to the cold. Stable microtubules are thought to be essential for neuronal development, maintenance, and function. MAP6 is a major factor responsible for the intriguing stability properties of neuronal microtubules and is important for synaptic plasticity []. It regulates axonal growth during neuron polarization, which is controlled by a palmitoylation cycle []. MAP6 interacts with TMEM106B, and this interaction is crucial for controlling dendritic trafficking of lysosomes, presumably by acting as a molecular brake for retrograde transport []. TMEM106B is a major risk factor for frontotemporal lobar degeneration with TDP-43 pathology.
This family includes Transmembrane protein 106A/B/C, type II transmembrane proteins which have homology to the late embryogenesis abundant-2 (LEA-2) domain []. TMEM106A has been identified as a key factor to regulate macrophage activation and a tumor suppressor in gastric, renal cancer and nonsmall-cell lung carcinoma (NSCLC), being an interesting therapeutic target for the management of NSCLC [, ]. TMEM106B localises to late endosomes and lysosomes, and it is involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking via its interaction with MAP6 []. Its overexpression is associated with familial frontotemporal lobar degeneration []. It has also been identified as a protein required for productive SARS-CoV-2 infection []. Structural analysis of LEA-2 domains revealed that they have a long, conserved lipid-binding groove, implying that TMEM106B and its homologues, Vac7 and Tag1 from yeast, may all be lipid transfer proteins in the lumen of late endocytic organelles.
