The Molecular Motor KIFC1 Associates with a Complex Containing Nucleoporin NUP62 That Is Regulated During Development and by the Small GTPase RAN1

Abstract

KIFC1 is a C-terminal kinesin motor associated with the nuclear membrane and acrosome in round and elongating spermatids. This location in developing spermatids is consistent with possible roles in acrosome elongation and manchette motility or both. Here we describe the association of the KIFC1 motor with a complex containing the nucleoporin NUP62. Formation of this complex is developmentally regulated, being absent before puberty and appearing only after nuclear elongation has begun. In addition, the integrity of this complex is dependent on GTP hydrolysis and the GTP state of the small GTPase RAN. Concomitant with the association of this motor with the NUP62-containing complex is an apparent reorganization of the nuclear pore with loss of NUP62 from larger complexes containing other nucleoporins. The association of KIFC1 with a component of the nuclear membrane is more consistent with a role for this motor in acrosome/manchette transport along the nuclear membrane than for a role for this motor in transport of vesicles along the outer face of the manchette.

Kif5B and Kifc1 Interact and Are Required for Motility and Fission of Early Endocytic Vesicles in Mouse Liver

“…Because these data indicated the presence of a minus-enddirected kinesin on mouse early endocytic vesicles and Kifc2 was absent, we considered the presence of other minus-end kinesins, of which only four others have been described previously (Yang et al, , 2001a(Yang et al, ,b, 2006Navolanic and Sperry, 2000;Noda et al, 2001;Miki et al, 2003;Yang and Sperry, 2003;Zhang and Sperry, 2004). Within this group, Kifc1 and Kifc3 were associated with membranous organelles Navolanic and Sperry, 2000;Noda et al, 2001;Yang et al, 2001bYang et al, , 2006Yang and Sperry, 2003;Zhang and Sperry, 2004), whereas Kifc4 and Kifc5 were seen in mitosis where they play a role in chromosome movement Zhang and Sperry, 2004). Consequently, we looked for the presence of Kifc1 and Kifc3 on mouse early endocytic vesicles.…”

“…Aside from Kifc2, only four other minus-end kinesins, Kifc1, -3, -4, and -5, have been described in mammals (Yang et al, , 2001b(Yang et al, , 2006Yang and Goldstein, 1998;Navolanic and Sperry, 2000;Miki et al, 2001Miki et al, , 2003 Noda et al, 2001;Xu et al, 2002;Yang and Sperry, 2003;Zhang and Sperry, 2004). Kifc1 and Kifc3 were found to be associated with membrane-bound intracellular organelles (Yang and Goldstein, 1998;Hoang et al, 1999; Noda et al, 2001;Xu et al, 2002;Yang and Sperry, 2003;Zhang and Sperry, 2004;Yang et al, 2006), whereas Kifc4 and Kifc5 are primarily active in mitosis Zhang and Sperry, 2004). As seen in Figure 5, immunoblot analysis showed that Kifc1 and Kifc3 were both present in liver and brain of wild-type and Kifc2 knockout mice.…”

The overexpression of KIFC1 was associated with the proliferation and prognosis of non-small cell lung cancer

“…The overexpression of KIFC1 was associated with the proliferation and prognosis of non-small cell lung cancer 5-year survival rate in the United States for lung cancer is 15.6% (4), the data of age-standardized 5-year relative survival is 15.4% in China (5) and has been unchanged for decades despite surgical advances and new antitumor drugs. Therefore, the importance of further understanding the molecular mechanisms underlying tumor cell proliferation cannot be overemphasized.…”

“…Research shows that KIFC1 participates many physiological and pathological processes. Such as, KIFC1 is associated with the nuclear membrane and acrosome in round and elongating spermatids (15) and is required for chromosome congression and alignment during mitosis (16). Farina et al reported that depletion of KIFC1 significantly decreases double-stranded DNA transport, which might provide new insight for gene therapy and DNA-based therapy (17).…”

Makings of the Best Spermatozoa: Molecular Determinants of High Fertility

“…Jmjd1a, for example, is a regulator of histone modification through demethylation in the testes, and its deficiency induced many infertile symptoms, indicating the essential role in spermatogenesis (Liu et al, 2010). In spermatids, Kinesin family member C 1 (KIFC1) motor which is a member of the Kinesin-14 subfamily associates with nucleoporin-containing complex and is p o s t u l a t e d t o b e i n v o l v e d i n a c r o s o m e elongation and motility (Yang et al, 2006;Yang and Sperry, 2003). TLRR is a leucine-rich repeat protein which interacts with KIFC1 (Wang and Sperry, 2008).…”