Fez1 Antibody (Rabbit mAb) [F20M11] Datasheet

Biological Description

Specificity	Fez1 Antibody (Rabbit mAb) [F20M11] detects endogenous levels of total Fez1 protein.
Background	FEZ1 is the mammalian ortholog of the Caenorhabditis elegans protein UNC-76, a gene originally identified for its requirement in axonal outgrowth and fasciculation, and FEZ1 was subsequently isolated in a yeast two-hybrid screen specifically as a binding partner of the regulatory domain of protein kinase C zeta, establishing FEZ1 as a direct downstream target of PKCζ signaling. In COS-7 cells, FEZ1 partitions between cytosolic and membrane-associated pools, and phosphorylation of FEZ1 by PKCζ drives redistribution of the membrane-bound fraction into the cytosol, while in PC12 cells this same PKCζ-dependent phosphorylation of FEZ1 stimulates neurite outgrowth, directly linking a single phosphorylation event to a defined change in both subcellular localization and neuronal differentiation behavior. FEZ1 functions structurally as a bivalent cargo adaptor, homodimerizing through its N-terminal region while engaging kinesin motor proteins and additional cargo-associated partners through its C-terminal region; nuclear magnetic resonance analysis shows that this N-terminal homodimerization occurs with the two FEZ1 chains oriented in an antiparallel topology, and biochemical characterization confirms the dimer is further stabilized by an intermolecular disulfide bond formed at a specific cysteine residue within the dimerization interface. This bivalent adaptor architecture is functionally conserved with the C. elegans UNC-76 protein, since UNC-76 similarly binds directly to the C-terminal tail domain of conventional kinesin heavy chain, forming a stable complex in vivo, and loss of UNC-76 function produces locomotion and axonal transport defects that phenocopy kinesin loss-of-function mutants, with UNC-76 additionally showing dosage-sensitive genetic interactions with both kinesin heavy chain and kinesin light chain mutations, together indicating that UNC-76/FEZ1 and kinesin-1 operate within a shared, mechanistically coupled transport pathway rather than through independent, parallel routes. FEZ1-SCOCO adaptor complex, using cross-linking mass spectrometry, small-angle X-ray scattering, and computational modeling, identifies an interaction interface consistent with that previously demonstrated for the UNC-76-UNC-69 complex in C. elegans, and this evidence supports a heterotetrameric assembly model for the transport machinery, indicating that FEZ1 recruits multiple adaptor partners into a single higher-order complex rather than functioning purely as a monomeric or dimeric kinesin linker.

Specificity

Fez1 Antibody (Rabbit mAb) [F20M11] detects endogenous levels of total Fez1 protein.

Background

FEZ1 is the mammalian ortholog of the Caenorhabditis elegans protein UNC-76, a gene originally identified for its requirement in axonal outgrowth and fasciculation, and FEZ1 was subsequently isolated in a yeast two-hybrid screen specifically as a binding partner of the regulatory domain of protein kinase C zeta, establishing FEZ1 as a direct downstream target of PKCζ signaling. In COS-7 cells, FEZ1 partitions between cytosolic and membrane-associated pools, and phosphorylation of FEZ1 by PKCζ drives redistribution of the membrane-bound fraction into the cytosol, while in PC12 cells this same PKCζ-dependent phosphorylation of FEZ1 stimulates neurite outgrowth, directly linking a single phosphorylation event to a defined change in both subcellular localization and neuronal differentiation behavior. FEZ1 functions structurally as a bivalent cargo adaptor, homodimerizing through its N-terminal region while engaging kinesin motor proteins and additional cargo-associated partners through its C-terminal region; nuclear magnetic resonance analysis shows that this N-terminal homodimerization occurs with the two FEZ1 chains oriented in an antiparallel topology, and biochemical characterization confirms the dimer is further stabilized by an intermolecular disulfide bond formed at a specific cysteine residue within the dimerization interface. This bivalent adaptor architecture is functionally conserved with the C. elegans UNC-76 protein, since UNC-76 similarly binds directly to the C-terminal tail domain of conventional kinesin heavy chain, forming a stable complex in vivo, and loss of UNC-76 function produces locomotion and axonal transport defects that phenocopy kinesin loss-of-function mutants, with UNC-76 additionally showing dosage-sensitive genetic interactions with both kinesin heavy chain and kinesin light chain mutations, together indicating that UNC-76/FEZ1 and kinesin-1 operate within a shared, mechanistically coupled transport pathway rather than through independent, parallel routes. FEZ1-SCOCO adaptor complex, using cross-linking mass spectrometry, small-angle X-ray scattering, and computational modeling, identifies an interaction interface consistent with that previously demonstrated for the UNC-76-UNC-69 complex in C. elegans, and this evidence supports a heterotetrameric assembly model for the transport machinery, indicating that FEZ1 recruits multiple adaptor partners into a single higher-order complex rather than functioning purely as a monomeric or dimeric kinesin linker.

Usage Information

Application

WB, FCM, ELISA

Dilution

WB	FCM
1:1000	1:500

Reactivity

Human, Rat, Mouse

Source

Rabbit Monoclonal Antibody

MW

45 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/24116125/
https://pubmed.ncbi.nlm.nih.gov/12925768/

Fez1 Antibody (Rabbit mAb) [F20M11]

Biological Description

Usage Information

References

Application Data