Table 4.

Microtubule (MT) binding and regulating proteins^*

Functional type of MT binding proteins	MT binding or regulating protein	Localization on MT and functions	Characteristic domain and binding partner	Phenotypes of KO and KD
MT stabilizing/ polymerizing proteins	End binding protein family (EB; e.g., EB1, EB2, EB3)	A +TIP protein, binding to the plus (+) end (i.e., growing end) of MTs [190], induced MT stabilization [191]	A calponin homology (CH) domain and end binding homology (EBH) domain [192]; interacted with mDia and APC.	In mouse fibroblasts, EB1 depletion led to a reduced MT growth time [193]; EB1 KD led to an increase in MT dynamics [194]
	Cytoplasmic linker protein family (CLIP; e.g., CLIP170 CLIP115)	Binding to the plus end of growing MTs [195], preventing catastrophe or promoting MT rescue events [196, 197]	Cytoskeleton associated protein/glycine-(CAP-Gly) rich domain mediated the interaction between MTs and EB1 [198]	Male CLIP-170 KO mice are subfertile, and produced sperm with abnormal heads [199]
	CLIP-associating protein family (CLASP; e.g., CLASP 1, CLASP 2)	Binding to the MT plus end tracking; stabilizing MTs [200]	CLASP proteins contained SxIP motifs at central region and TOG domain at the N- terminal region [200, 201]	The neuromuscular junction in adult Clasp2 KO mice was abnormal due to the mis-localization of CLIP-170 [202]; KD of CLASPs by RNAi led to reduced acetylated tubulin [203]
	Adenomatous polyposis coli family (APC; e.g., APC, APC2 also called APC-L)	APCs directly associated with MT plus end [204], promoted MT polymerization and stabilization [205]	Interacted with armadillo repeat domain (ARD) [206], MT interaction domain APCp1, and EB1 interaction domain SxIP [207].	APC conditional KO in mice induced accumulation of β-catenin in astroglia; morphological changes in Bergmann glia [208].
	The tumor overexpressed gene) family (TOG; e.g., ch- TOG)	TOG proteins localized to MT plus ends by promoting MT elongation [209]	TOG domain containing protein. The Xenopus TOG, XMAP215, was identified as a MT polymerization promoting protein [210, 211]	Mice with TOG conditional KO in hippocampal neurons exhibited hyperactivity with impaired short term habituation [212]
	Calmodulin- regulated spectrin- associated protein family (CAMSAP, such as CAMSAP1, CAMSAP2, CAMSAP3)	A -TIP, CAMSAP bound to the MT minus (−) ends to stabilize MTs against disassembly induced by MT depolymerases [213, 214]	Presence of C-terminal CKK domain [215]	PTRN-1 (the C. elegans member of CAMSAP) mutants led to impaired regenerative re-growth of axons; number of dynamic axonal MTs were also induced [216]
MT severing proteins	Katanin (katanin p80 or KATNB1, katanin p60)	Katanin simulated MT plus-end depolymerization [217]. Katanin was shown to be a heterodimer of a p60 severing enzyme and a p80 regulatory subunits [218]	C-terminal region contained AAA (ATPase associated with diverse cellular activities) ATPase domain; also present is the microtubule interaction and trafficking (MIT) domain [219]; katanin also localized to mitotic spindle poles in mammalian cells that regulated spindle structure and chromosome movement [220]	Katanin mutation in C. elegans led to failure to form a bipolar spindle [221]; katanin p80 mutation in male mice led to sterility [129]; some genetic variants of KATNB1 also led to oligoasthenoteratozoospermia (typified by low sperm number, abnormal sperm shape and poor motility) in human males [130]
	Spastin (SPG)	Involved in MT severing at the minus-end [217, 222]	Contained an AAA ATPase domain, and MIT domain at N-terminal region [223]	Spastin KO mice were sterile, exhibited progressive axonal degeneration in central nervous system that led to a late and mild motor defect [224]; mutations in SPG4 gene led to autosomal dominant hereditary spastic paraplegia (HSP) in humans [225].
	Fidgetin (FIGN; consisted of FIGN, FIGNL1, FIGNL2)	Fidgetin stimulated MT minus-end depolymerization [217]	Containing AAA ATPase domains [217].	Fidgetin KD induced MT-dependent enlargement of mitotic centrosomes and an increase in the number and length of astral MTs [226].
MT motor proteins	Kinesin (there are 45 members of kinesin, composed of 14 classes, and classified into three types based on the relative position of the motor domain) [227]	A plus-end-directed motor protein [228]; kinesin 8s (Kif18A, Kif18B, Kif19) and kinesin 13s (KIF24, Kif2A, Kif2B and Kif2C/ MCAK) also served as MT depolymerization proteins [229-231]	Kinesins possessed motor domain and one or more coiled-coil domain [228]	kif1b−/− KO mice had defects in both sensory- and motor-nerve function, and died at birth due to nervous system defects [232]
	Dynein	A minus-end-directed motor protein [233], composed of heavy, intermediate, light intermediate, and light chains [234]	The heavy chain contained the motor domains with six AAA ATPase domains and a MT-binding stalk, dynein interacted with dynactin [234]	Mutations of several dyneins caused immotile cilia syndrome, human males with immotile cilia syndrome were found to be sterile [235, 236]

^*This Table is not intended to be exhaustive, only selected representatives are shown here. Abbreviations used: AAA ATPase domain, ATPase associated with diverse cellular activities ATPase domain; CKK, CAMSAP1, KIAA1078 and KIAA1543 domain which binds to MT; FIGN, fidgetin; FIGNL1, fidgetin-like 1; KD, knockdown; KO, knockout; MT, microtubule; −TIP, microtubule minus-end tracking protein; +TIP, microtubule plus-end tracking protein; SxIP motif, Ser-x-Ile-Pro motif; PTRN-1, PaTRoNin (microtubule-binding protein) homolog 1; RNAi, RNA interference.